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Full text of "Opening Statements Before the Committee on Appropriations"






OPENING STATEMENTS 










OS. DEPARTMENT OF HEALTH, EDUCATION, AND. WELFARE 

PUBLIC HEALTH SERVICE 

NATIONAL WkfltTtiS W HEALTH 








Natrona! Institutes of H« 
and 



OPENING STATEMENTS 
for the 
National Institutes of Health 

In Connection with 
Appropriation Requests for Fiscal Year 195$ 






pH,5,. National Institutes of Health, 
Public Health Service 
U. S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE 






15 i 



073641 



SUMMARY OF OPENING STATEMENT 
by 
Director, National Institutes of Health 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1955 ESTIMATE 
for 
"General Research and Services, National Institutes of Health" 



The past year has "been an active and productive one with 
many developments in the NIE programs for research, the training 
of scientific manpower, and research facilities . 

195 7 Grant Progr ams. The proportion of research applica- 
tions rejected in fiscal year 1957 was the same as in previous 
years, indicating continuation of high standards. New research 
grants approved after the Fall Council meetings commit support 
for an average 3*2 years, an increased in the stability of 
support as compared with the 1951 average of 1.8 years. 

Divisio n of Research Gr ants. The Division is a central 
point for coordination of the grants and fellowships program. 
The Division also administers research grant and training 
programs in areas which do not fall within the categorical 
responsibility of any of the Institutes. Such programs are 
underway in basic research, research facilities construction, 
and a new fellowship program in the preclinical sciences. 

Division of Biologies Standard s. The Division's 
regulatory and research programs nave been strengthened. Its 
work is aimed toward assuring the safety, purity, and potency 
of more than 250 biological products. 



- 2 - 



Services in Support of Research at Bethesda . The Division 
of Research Services and the Division of Business Operations pro- 
vide most of the non- clinical resources and services for the 
complex NIH program. Clinical services are provided for all the 
Institutes by the Clinical Center, The clinical research 
programs at Bethesda gained momentum, but the nursing shortage 
continues to be a limiting factor. 

Construction at Bethesda . Construction of two buildings 
for experimental animals, to be used temporarily for office 
space, are scheduled for completion in the fall. Construction 
of the new laboratory for the Division of Biologies Standards 
is expected to start in July, and a design contract has been let 
for the surgical addition to the Clinical Center. Plans are 
being developed for a permanent office building and a dental 
research building. 

Research Facilities Construction Grants . The new program 
for these grants, under the Health Research Facilities Act of 
195^; is covered in a separate opening statement since the 
appropriation to finance this program is carried as a separate 
item in the budget . 

Areas of General Program Interest , A series of supple- 
mentary documents, "Research Highlights of 1956/' are offered 
for the record by each of the Institute Directors and concern 
progress in their fields. 



- 3 - 

Medical scientific training has been aided through new 
and continuing programs, with over 5.' 000 individuals receiving 
support this year under training grant and fellowship programs. 
The program at Bethesda for visiting scientists has been 
strengthened. 

Another major development has been that of industry- 
participation in certain developmental research, such as the 
Cancer Chemotherapy program. 

Other important developments include the establishment 
of a Center for Research on Aging at NIH and a Psychopharmacol- 
ogy Service Center by the Rational Institute of Mental Health; 
and the emergence of long-term collaborative research projects, 
as for example in programs of the National Institute of 
neurological Diseases and Blindness. Also begun during the 
year was a program to aid the translation of Russian medical 
scientific literature for American scientists. 

Proposed 19^8 Increases . The figures and factors con- 
cerning these increases and relationships with 1957 appropri- 
ations and expenditures are presented, with major points and 
considerations underlying them. 



OPENING STATEMENT 
by 
Director, National Institutes of Health 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"General Research and Services, National Institutes of Health" 



Mr. Chairman and Members of the Committee: 

It is a pleasure to appear before you again in connection 
with budget proposals for the National Institutes of Health. 

I should like first to make several general points as 
background for that part of my report dealing with the substance 
of the medical research and manpower programs initiated or 
strengthened by Congress in the last session and placed in the 
administrative custody of the National Institutes of Health. 

As all of us know, support of medical research from both 
private and public sources has increased steadily since World 
War II. The United States this year is investing in the neighbor- 
hood of $300 million for medical research, with strong and growing 
support from both public and private sources. The appropriaticn 
level for the National Institutes of Health represents an important 
segment of the total national research effort against disease, 
and the policies and practices which we follow in executing the 
budget appropriated by Congress, have a great deal to do with 
setting the general tone of free and productive inquiry in 
this country. 



By its actions in the last decade, the Congress has given 
us a great deal of freedom to advance medical research according 
to our knowledge and perception of its needs. With this freedom 
goes the responsibility to use the expanding opportunity with the 
utmost effectiveness. 

The decade just past stands out as a period in which the 
existing pool of competent scientists --augmented by physicians 
drawn to research and "by physical scientists who became attracted 
to the rapidly developing fields of biological science- -was for 
the first time approaching an adequate level. If this pattern is 
maintained during the decade ahead, research manpower and research 
facilities and research funds will emerge as factors of comparable 
significance in medical research program planning. 

Such planning has both immediate and long-range goals. The 
immediate task is to make full and effective use of today's resources 
for medical research, so that no promising lead remains unexplored 
and no useful finding unapplied in medical and public health practice. 
But at the same time we must be concerned with what is ahead. It 
takes time to build a field of science, to expand the pool of 
trained manpower, to construct buildings. 

These timing processes can be quite complex and certainly 
have a material effect on the current programs of the National 
Institutes of Health. For example, the Congress has made grant 
funds available to the Public Health Service for the construction 
of research facilities, an action which may temporarily and in 



- 3 - 

part shift the most urgent pressure point to the manpower area. 
If , however, this action had "been delayed, it is predictable that 
shortage of laboratory space would have progressed from the serious 
to the critical stage. 

Another current program activity that looks to the future 
is the training of scientific manpower. This program has increased 
substantially in the last two years, including a 100 percent increase 
from 1956 to 1957. A wide range of mechanisms are utilized to meet 
the needs of the specialized fields. Progress related to our train- 
ing activities will be interwoven in the testimony of each National 
Institutes of Health witness who will appear before you. 

The last general observation I wish to make before getting 
down to specifics has to do with the importance of gaining an 
accurate appraisal of the general scientific situation. At any 
given time, there are areas of science that are ripe for a rapid 
forward advance. These rapid advances generally depend upon a 
finding that opens up a whole new area of study. Thus applied 
findings result in improvements ; but basic findings result in 
revolutions. We are now in the midst cf establishing the basis 
for revolutions in medical science, and in other areas we are 
seeking improvements. From this viewpoint, the joint task of the 
Congress, the scientific community, and NIH as the Public Health 
Service's specific administrative agent in this field for the 
executive branch, is to design Federal support so that there is a 
sound balance between the research that yields improvements and 
the research that yields revolutions. At the same time we have an 



obligation to cause research to face realistically and productively 
towards those groups of diseases that are of the greatest significance 
to society. The relevance of this consideration will emerge during 
the discussions by the several Institutes, whose programs contain 
large components of basic science and applied science, with a 
high degree of orientation toward the diseases and disorders which 
are their statutory responsibility. 

I feel sure you will find, as we have, that this has been 
an active and productive year for us, both in our own research 
and for the many thousands of scientists who have conducted research 
under our grants or been trained for research careers under NIH awards. 

I should like to share with you some of the successes and 
some of the problems during the year, 

LEVEL CF EXPENDITURES, 1957 GRANT PROGRAMS 

In making decisions on the increased level of support for 
the current year, the Congress made it abundantly clear that we 
were to support only sound research and research training projects. 
The 1957 appropriation for NIH was thus viewed by Congress as being 
of an order of magnitude which would permit optimal growth for each 
program without necessarily placing an arbitrary financial ceiling 
on any one of them. The basis for this principle is that the 
national interest is best served if medical research moves forward 
on all fronts to the limit of its capacity to produce effectively- - 
and that the Federal government has an essential role in this 
undertaking. 



- 5 - 

The key to the policy set by Congress is effective research. 
We transmitted the general guide set "by Congress to our scientific 
advisory groups. They have considered the availability of funds 
not as an invitation to recommend that research of low quality he 
approved, hut rather as an opportunity to ensure that no research 
of high caliber would go unsupported. During this fiscal year, the 
percentage of research applications considered unworthy of support 
has not decreased over earlier years , even though additional funds 
have become available. We have watched this figure carefully. The 
fact that the same proportion of applications have been rejected in 
this year as in earlier years, when a smaller volume of funds was 
available, seems to us to be the key figure proving that the 
standards of quality have been maintained. 

The credit for assuring the quality of the research supported 
should go to members of our Study Sections, Advisory Councils, and 
other consultative groups. These men and women of American science 
are performing a Herculean task in the review and recommendation 
of literally thousands of applications for research and training 
support. They serve with little compensation and virtually no 
recognition, performing a vital service for the entire scientific 
community. There are roughly 300 of these individuals who assist 
in the administration of our grant and award programs. Their efforts, 
and the points of view they bring with them to their advisory tasks, 
serve to maintain these programs as truly national in scope and 
in the image of free and productive research endeavor. 



6 - 



There will be some unexpended funds from our appropriations 
this fiscal year. It is difficult to he certain precisely how 
large these balances may be, Early last fall, we projected that 
all but about $10 million would be expended, almost all the savings 
being in the research grant area. We have been advised by the 
Secretary that the full amount cf our total appropriation remains 
available to us as needed. The governing factor here is the 
number, the quality, and the dollar amounts of recommended grant- 
applications within each category. His concern, as it is ours, 
and as I am sure it is yours, is that the high standards for 
review be maintained, 

STABILITY OF RESEARCH SUPPORTED BY GRANTS 
The additional funds made available during this fiscal year 
have made it possible for us to move towards another major objective. 
Scientists need stable support if they are to work effectively, 
The new grants approved after the last round of Advisory Council 
meetings committed support for an average of 3-2 years. In 1951; 
the comparable figure was 1,8 years, This increased stability 
of support is a major long-range goal of the NIH research grant program 

It must be borne in mind that ten years of experience have 
taught us that about eighty percent of the grants supported in any 
one year will request renewal in the following year. We feel it 
advisable to avoid committing funds in one year at a level which 



- 7 - 

will make it impossible for us to sustain continuity and at the 

same time give new investigators a fair chance in the following year, 

THE DIVISION OF RESEARCH GRANTS 

As you know, these hearings call for the Directors of each 
of the seven Institutes to come before you and discuss their programs. 
These men are well known to most of you. The youngest of them in 
point of service has come before this Committee on at least three 
previous occasions. They have, both individually and collectively, 
turned in a truly outstanding job of research administration during 
a period of rapid change and growth. I know you will find their 
presentations interesting and informative. I will not discuss the 
specific accomplishments and problems and budget proposals of 
these seven Institutes. However, there are some general activities 
which relate to the organization as a whole rather than to the 
individual Institutes. I should like to discuss them briefly. 

We have, for example, a central point for the coordination 
and mechanics of the grant and fellowship programs of the Institute. 
We also have important research and training programs in areas which 
do not fall within the categorical responsibility of any of the 
Institutes. These functions are performed by the Division o^ 
Research Grants. 

The receipt, processing, review, and payment of research 
grants, fellowships, and related extramural activities is a vitally 
important function. The essence of this process is individual 



8 



consideration of each application "by competent professional people. 
The Division is staffed, and structured to provide this service 
so that the grantee, his institution, our review and evaluation 
groups, and the Institutes are linked in productive and efficient 
partnership. 

The support through the Division of Research Grants of basic 
studies and certain training activities includes the new fellowship 
program in the preclinical sciences. The selection of outstanding 
individuals for support under this program premises to make a major 
contribution to the research component of the medical snhools. 
The Division of Research Grants also administers the experimental 
teaching program. Selected medical schools will on an experimental 
basis determine how to train selected students more effectively in 
the basic physical and biological sciences and in the modern 
research designs which are becoming vital ingredients of present- 
day medical research. The Division administers the Health Research 
Facilities Act, under which $30 million is awarded in matching 
grants for each of three years to assist in the construction and 
equipping of research facilities in medical schools, universities, 
and other research centers. It carries out our predoctorate and 
postdoctorate fellowship program, which since its inception has 
given more than 5; 000 individuals training in research techniques 
and in specialized biological research fields. It provides grant 
funds for fundamental studies in such areas as toxicology, pharmacology, 
anatomy, physiology, and pathology. Finally, the Division administers 
for other components of the Public Health Service research programs 



- 9 - 
in such areas as hospital facilities, .nursing, and air pollution* 

Thus the Division of Research Grants is the meeting place 
for vitally important basic studies, for extensive training 
activities, and for a number of experimental programs that are 
exploring ways to select, train, and retain scientific research 
manpower in the medical school and university environments, 

A fuller discussion of the activities of the Division of 
Research Grants is contained in Attachment A to this statement. 

T H5 DIVISION OF BIOLOGIC S STANDARDS 

Our statutory responsibility to regulate and control biological 
products used in interstate and foreign commerce is centered in 
the Division of Biologies Standards. Developments in this field 
have been extremely rapid, and the laboratory has been required 
to strengthen and expand both its regulatory and its research 
aspects in order to carry out its mission. A new laboratory build- 
ing has been authorized for this Division and funds for its 
construction have been appropriated. The task of the Division's 
staff is to assure that there are adequate manufacturing controls 
to safeguard the safety, purity, and potency of more than 250 
biological products now used in medical and public health practice. 
With the advent of new virus vaccines and other modern biological 
products, the ties between the Division's control functions and 
its research activites become more and more apparent. Major 
contributions in the development, testing, mode of action, and 



- 10 - 

limitations of new biological products are a by product of the 

sh. 

Further information concerning the Division of Biologies 
Standards will be found in Attachment B to this statement. 

SERVICES IN SUPPORT OF RESEARCH AT BETHESPA 

Three organizational units at the National Institutes of 
Health provide services and facilities for the research 
activities at Bethesda. Two of these units --the Division of 
Research Services and the Division of Business Operations --provide 
the bulk cf the non-clinical resources and services for the complex 
research programs of the Institutes. 

The third organizational unit which provides central services 
of a highly specialized kind is the Clinical Center --which, as 
you know, is both a structure and a program permitting each Institute 
to engage in clinical investigations. Like the Division of Research 
Services and the Division of Business Operations, the Clinical 
Center is financed cooperatively by the seven Institutes, 

The clinical research programs have gained direction and 
momentum with almost unprecedented speed. We have excellent 
clinical investigative staffs. Their professional supporting aides 
-and services are of a high order of competence. We accept patients 
only upon referral from a physician, and practicing physicians 
have been most cooperative in sending patients to us. The clinical 
programs have continued to be highly productive, as reflected by 



- 11 - 

a number of significant findings which will be detailed for you 
by the Institute Directors. There has been satisfactory progress 
toward fulfillment of the objectives for which the Clinical Center 
was planned and built. 

Several problems, however, still confront us. Because of 
the key role of Congress in establishing the Clinical Center and 
because of the special interest of this Committee in its effective 
operation, I want to explain them. 

The most difficult and complex of these problems is the 
question of bed occupancy and the shortage of nurses in the Clinical 
Center. As you know, estimates of bed activation and bed occupancy 
play an important role in our budget formulation processes. I 
should like to emphasize here that the principal determinant of 
bed occupancy in the Clinical Center is the complexity and extent 
of the clinical investigation projects arising in the research 
programs of the several Institutes. Thus, some clinical projects 
may involve research activities and patients requiring major 
amounts of nursing and associated clinical services. All nursing 
positions supportable under budget levels may be required and more 
to provide the nursing services needed, yet considerably less than 
the full number of beds available may be utilized. Other projects 
may demand much less activity per patient, but a larger number of 
research patients may be involved. Bed occupancies under such 
conditions would therefore be high. 



- 12 - 

Under these circumstances, bed occupancy rates do not have 
the same meaning and relationship as they do when applied to the 
typical general hospital. For general hospitals, the percent of 
bed occupancy may, quite properly, be considered to denote the 
degree to which staff, facilities, and services are being effectively 
utilized. The extension of this approach to the Clinical Center 
is, we believe, inaccurate and misleading. In fact, quite the 
reverse is true - the number of beds occupied represents the 
maximum level of occupancy which full utilization of available 
nursing staffs and related clinical services can support in 
carrying out the research activities involved. 

The availability of nursing, therefore, is a prime factor 
in determining the nature and extent of the clinical research 
projects undertaken. The continued shortage of nurses has been 
troublesome, because of the limitations it has represented in 
the development of the clinical research program. The fact that 
this has restricted occupancy and retarded projected bed activation 
schedules has been disturbing, not in terms of efficiency or the 
substance of the research being done, but only because of our 
desire to mount a maximum clinical research effort. 

I have discussed this problem in detail in order that 
factors leading to changes in the forecasted occupancy rates for 
the Clinical Center be understood. Our goal is, of course, the 
maximum use of the clinical research potential represented by the 
Clinical Center. This, however, is more a function of the character 
of the clinical research program and its requirement for 



- 13 - 

professional personnel than it is an arbitrary number of beds 
occupied by patients. 

Another problem I should mention has to do with the i-:inds 
of patients under study in the Clinical Center and the processes 
by which they are selected. The Clinical Center is large and 
nationally prominent, It is understandable if there is a general 
assumption that in the Clinical Center there should be a study 
on virtually all of the diseases and disorders with which man is 
afflicted« This, of course, is not and cannot be the case. To 
be sure, some aspects of most of the major disorders are being 
investigated. But many other aspects of the same diseases carr.ot 
be under study simultaneously. For example, it would be 
theoretically possible for leukemia and cancer of the thyroid and 
cancer of the prostate to be under study, while breast cancer and 
lung cancer and skin cancer might no 4 : , The governing factors 
are evident: a sound study cannot exist unless there are promising 
research leads, a competent staff without other research obligations, 
and the resources needed to mount and sustain a study of the 
magnitude and duration that has the best chance of yielding 
productive findings. We, therefore, must often reject referrals 
for admission when there is no suitable research program for 
or current interest in the condition involved. 



- Ik - 

CONSTR UCTION AT BETPESBA 

There are six construction projects at Bethesda in which 
this Committee has evidenced special interest. None of these is 
the subject for an appropriation request at this time, but I 
think you may wish a report on their current status » Progress 
on these projects has not, quite frankly, been as rapid as we 
at first hoped and anticipated; however, it has been steady, and 
each project promises to add an important element to our research 
environment, 

Nearest completion is the Residential Treatment Center — 
a sort of "Halfway House" for disturbed children now under re- 
search study by the National Institute of Mental Health. This 
cottage is designed to meet the needs of children who are ready 
to leave the restrictions of institutional care but not yet ready 
to return completely to the community. The structure is completed 
and is now being equipped to receive a group of children who have 
been under sxudy in the Clinical Center for some time. Occupancy 
is scheduled for April, 

A second construction project at Bethesda is the new lab- 
oratory to house the regulatory and the research functions of the 
Division of Biologies Standards. It will be similar in size and 
basic structure to the other laboratory buildings at the National 
Institutes of Health. The design contract with an outside contractor 
has been let, and a total of $3- 5 million was appropriated in 
Fiscal Year 1956 for its construction. According to present con- 
struction schedules, the laboratory should be started in July 1957 
and ready for occupancy in March 1959. 



" - 15 - 

Another building project at Bethesda really consists of two 
identical structures designed for the breeding and maintenance of 
experimental animals. We must use them temporarily to meet a part 
of our acute and immediate need for more office space, primarily 
to administer the expanding research grant and training programs. 
Work is in progress on this project, and we hope for completion 
sometime next fall, $1,371,000 have been appropriated for this 
purpose, 

A fourth construction project is the erection of additional 
surgical facilities as a wing of the Clinical Center. $1.6 million 
were appropriated for this project in Fiscal Year 195&. The design 
contract has been let to York and Sawyer of New York, one of the 
outstanding hospital architects in the country. The surgical wing 
is planned to accommodate cardiac surgery, neurosurgery, and 
certain auxiliary functions related to surgery „ Present estimate 
for progress on this facility calls for construction to begin in 
January 1958 and for the structure to be completed about January 

1959. 

The last two of the six construction projects at Bethesda 
to which I referred earlier are the new laboratory buildings for 
the National Institute of Dental Research and the permanent office 
building. Planning for these projects is going forward under 
appropriations of $200,000 for the dental research building and 
$300,000 for the permanent office building. As you know, we are 
not including in our request before this committee funds for 



- 16 - 

construction of these "buildings at this time. This is based on 
the decision of the Administration to defer for this year all 
new construction projects except those of the most critical national 
importance. As a consequence, the dental research building and 
the permanent office building have not been included in the budget 
submitted by the President for Fiscal Year 1958* 

GRANTS FOR THE CONSTRUCTION OF HEA LTH RESEA RCH FACILITIES 

The 8^th Congress enacted into law the Health Research 
Facilities Construction Act (Public Law 835 )• This Act provided 
that $30 million be expended on a matching basis during each of 
three years to support the construction and equipping of labora- 
tories and related research facilities among non-Federal institu- 
tions. The National Institutes of Health was called upon to 
administer this new program. I am pleased to be able to report 
actions which confirm the essentiality of the program and the 
acuteness of the problem it will help alleviate, 

In quick succession following the action of Congress on this 
program, we designed our administrative structure, established a 
strong and representative Advisory Council, prepared and promulg- 
ated regulations, and informed medical schools, universities, and 
other research centers of the availability of funds and the con- 
ditions under which funds could be made available. 

By January 15, 1957, applications or letters of intent to 
apply had been received from 228 institutions totaling over 
$116, 600, 000c More than $25 million of the $30 million available 



- 17 - 

for this year had been utilized in the support of 80 projects. 

Such a response is a corroboration, if such were needed, that 
this program will assist materially in resolving a serious handicap 
of many non-Federal research centers. The outcome of the three-year 
program under Public Law 835 seems clears the needs are great; 
matching funds are available or can be made available; and the 
mechanisms are sound. 

As required by the law establishing this program, a full report 
on progress through December 31> 1956> has been submitted by the 
Surgeon General for transmission to the Congress. 

Since the appropriation request to finance this program is 
carried as a separate item in the budget, I have prepared a separate 
opening statement which is attached to this statement. I shall, of 
course, be glad to discuss the program in some detail if the 
committee wishes. 

AREAS OF GENERAL PROGRAM INTERE ST 

At this point I should like to mention briefly several 
significant program developments which have been part of our progress 
during the past year* 

The details of that progress will emerge both during the 
testimony of the Institutes and in a series of supplementary documents 
prepared for these hearings and called Research Highlights of 195&. 
I mention these background materials, Mr, Chairman, because--with 
your permission--we should like to offer them for the record 
individually as the witnesses are called. I have here, for 
example , a statement containing some highlights from the Division 



18 



of Research Grants, the Division of Biologies Standards, the 
Clinical Center, and other units not contained within the 
categorical Institutes, and I respectfully request that it be 
accepted for the record. 

One of the outstanding developments during the past year 
has been the emphasis on training manpower for careers in medical 
science. The funds available to us for training activities of 
all kinds were double the amount available in Fiscal Year 195& 
(from $17.3 million to $33*7 million). Thus we were able to 
strengthen existing programs; to give special attention to acute 
shortage areas (such as neurology, ophthalmology, rheumatology 
and psychiatry); and to design several new training programs 
slanted primarily toward strengthening research in the basic 
sciences as a component of the medical school environment, A 
total of over 5,000 individuals will have received either full or 
part-time support this year under our training grant and fellow- 
ship programs. At the same time, we have taken steps to increase 
the use of our own laboratories in Bethesda as a resource for 
training scientists from outside, and we are making a conscious 
effort to broaden the training of our own staff by providing 
opportunities for them to study in other laboratories. We also 
hope to secure for our scientists sustained association with the 
best brains from the rebuilt European laboratories by bringing to 
this country for a year or two, some of the most brilliant of the 
post-war generation of scientists. These many and varied training 
activities reflect our belief that the trained and creative mind 
is the key to progress against disease. 



- 19 - 

Another major development has been the conclusion that 
industry participation is a necessary ingredient in certain of our 
developmental research. This conclusion was first reached in 
connection with the Cancer Chemotherapy program, which is centered 
on the development and testing of many thousands of chemical agents 
in an effort to identify those with promising activity against 
human cancer. Medical schools and universities are not constituted 
to do this kind of job to any great extent; but industry is, and 
so we have worked long and hard to make our program aims and needs 
known to industry, and have elicited their understanding and willing- 
ness to cooperate. On the basis of this, we are now developing 
suitable industrial contract mechanisms and seeking to resolve 
questions of patents, confidentiality, profit margins, and so on. 

Then, too, we see the Cancer Chemotherapy National Service 
Center concept spreading to other fields a When a field has developed 
to a point which requires extensive developmental research or 
large-scale clinical evaluation, it becomes increasingly necessary 
to move toward patterns of support which depart from these which 
are used for the support of fundamental studies. And we may expect 
some of these other channels to be used as we move ahead with our 
programs in such fields as the evaluation of the tranquilizing, 
the hypertensive, and the oral antidiabetic drugs. A Psyehopharmacology 
Service Center has been established to spearhead the evaluation 
of the tranquilizing drugs, and more recently an NIH Center for 
Research on Aging has been set up to give leadership, guidance, 
and support to our activities in this field. While each of these 



- 20 - 

is different in some respects from the Cancer Chemotherapy 
Center, in all cases they perform staff functions and serve to 
coordinate and stimulate research instead of performing a direct 
operating function. The establishment of such programs within 
programs serves very necessary and useful purposes, and indeed 
may be the only way to initiate new programs with certain 
specialized characteristics. We must always measure the need with 
extreme care, however, lest by establishing such units we create 
an abnormal administrative mechanism which serves to fragment 
rather than consolidate Institute programs. 

Another program development of general interest is the 
emergence of long-term collaborative research projects as the 
mechanism of choice in achieving certain of our research 
objectives. For example, Dr. Bailey will describe to you later 
his Institute's organized effort, involving many institutions 
and many disciplines working under a central plan, to study 
cerebral palsy, mental retardation, and other crippling diseases 
which arise as a result of unknown and adverse biological factors 
that are operative before, during, and shortly after birth. 
Programs that are comparable in principle are found in the Mental 
Health field investigations, in study of new drugs against heart 
disease, and the Cancer Institute appraisal of the usefulness of 
exfoliative cytology in the early diagnosis of uterine cancer. 



- 21 - 

TRANSLATION OF SOVIET SCIENTIF IC LITERA TURE 

Those of you who were members of this Committee last year 
may recall our discussions of Russian science and the interchange 
of Russian and American literature in the medical and biological 
sciences, I am glad to be able to tell you that we have made 
substantial progress in the translation and dissemination of 
selected Russian scientific papers and abstracts. The first 
issues of two journals have been distributed to 300 libraries ; and 
a contract for the translation of six other journals has been 
awarded; we have agreed to translate papers selected as having 
special interest to the editors of ^0 American scientific journals, 
substantial blocs of Soviet abstracts are being translated and 
published under a grant to Excerpta Medica; and we have arranged 
for publication of a Russian-English medical dictionary and of a 
directory of Soviet research institutes. The continuation and 
extension of such activities will go far toward achieving a 
current understanding of the nature and direction of Soviet 
medical science, In this work, we are maintaining close liaison 
with the National Science Foundation and other groups actively 
engaged in the translation of scientific literature from the 
Soviet Union, 



- 22 - 
PROPOSED 1956 INC REASES OVER 1957 PROGRAM 

The budget proposal that is before you asks the appropriation 
of $190,2 million for the activities of the National Institutes 
of Health in 1958; exclusive of the Health Research Facilities 
Construction Program. This $190,2 million request compares with 
the $183.2 million appropriated for these same activities in 1957' 

When the Congress acted upon our appropriation for the 
current year, it pointed out its awareness that there are limitations 
on the speed with which the Nation* s medical research effort can 
be increased and emphasized its expectation that there should be 
no sacrifice in the scientific quality of the work the 
appropriation would support. 

Accordingly, before we could plan in any detail the 1958 
program now under consideration, we had to undertake an appraisal 
of how much of the 1957 appropriation might remain unspent under 
these criteria. Our autumn estimate was roughly $10 million, 
with most of the estimated savings in the research grant programs. 
When this fact, together with our detailed assumptions in support 
of it, was communicated to the Secretary of Health, Education, 
and Welfare, he advised us that the anticipated $10 million 
savings should be considered as available if our estimates proved 
low and if there were sound research projects which would remain 
unsupported unless the estimated savings were utilized. 

Thus the program increases from 1957 to 1958 are measured 
by the difference between our estimated expenditures in 1957 
($172.9 million) and our 1953 budget proposal ($190,2 million), 
or a total planned increase of $17.2 million. 



- 23 - 

The planned utilization of these increases over the 1937 
expenditures as we saw them early last fall are as follows: 



1956 1957 1958 
Actual Estimated Appropriation 
(All figures in millions) Obligation Obligation Requested 



TOTAL, National institutes 
of Health 


$ 98.1 


$172.9 


&190<2 


National Cancer Institute 


24.9 


44„3 


46.9 


National Heart Institute 


19.0 


31.5 


33.5 


National Institute of Mental 
Health 


18.1 


32.3 


35.2 


National Institute of Arthritis 


10.9 


16.0 


17.9 



& Metabolic Diseases 

National Institute of Allergy 

& Infectious Diseases 6.5 

National Institute of Neurological 

Diseases & Blindness 9«7 

National Institute of Dental 

Research 2.2 

Iloncaxegorical Research Grant 

and Training Activities 6.8 



In connection with the 1958 programming, I want to talk 
particularly to the question of the indirect costs to research 
institutions whose scientific staffs receive cur research grants 
for their individual projects. 



13.5 


17.4 


17.8 


18=9 


5.9 


6,4 


11.6 


14.0 



- 2^ - 

Granting agencies, both private and public, have long recognized 
that project grant awards must include funds to compensate the research 
institution, at least in part, for such indirect factors as utilities, 
space renovation, accounting, administration, and other costs related 
to the maintenance of the project in their environment. The exact 
amount of these indirect costs is difficult to establish, particularly 
when a formula is sought which can be applied fairly to all grants 
and all institutions. This matter has remained under constant review 
since World War II, and is even now under intensive review by a 
government -wide committee established under the auspices of the 
General Accounting Office and the Bureau of the Budget. During the 
first years of the grant program, until 195^ > we used 8$ of the grant 
amount approved in determining the indirect costs. Since 195^ > we 
have used 15$ as the factor. The budget that is before you for 1958 
contains funds which will permit an increase from 15$ to 25$, If 
this is approved, it will bring our indirect coaTt factor into line 
with the practices of government agencies providing the great bulk 
of funds for research. These agencies for some time have been using 
a factor of 25$ or higher for their research grants and research 
contracts. This provision will keep research grant funds from 
continuing to impose a serious drain on the institution's operating 
funds, which are already at a critical point. 

Of the 1958 increases, $6.8 million would be directed to the 
payment of up to 25$ rather than 15$ for indirect costs on research grants. 



- 25 - 

Other major program elements in the $17.2 million proposed 
increase over estimated 1957 expenditures are expansion of grant 
activities particularly in allergy but also in arthritis and in the 
non-categorical research areas ($3-3 million); $1.5 million for an 
essentially new program of special project grants in mental health,, 
under Title V of the Health Amendments Act of 195^; additional funds 
for the allergy and immunology training program just established this 
year ($650 .,000); a second increment in the planned five-year program 
for senior research fellowships in the preclinical sciences ($500,000); 
increases in certain of our direct operations at Bethesda ($1.2 million); 
and just in excess of $3 million for such factors as annualization 
of 1957 programs. Wage Board increases, Retirement and Social Security 
costs, and salaries in excess cf the 52 -week base. 

All of the other program areas would remain essentially at 
the level of 1957 expenditure. 

SUMMARY 

I believe, Mr. Chairman and members of the Committee, that 
the appropriations provided last year by Congress have been and are 
being effectively utilized. The basic underpinning of our National 
medical research effort has been strengthened; dramatic gains have 
been made on several fronts; there has been a farsighted investment in 
the future in the form of manpower and facilities; and research resources 
which have not been fully utilized are being developed and linked with 
the National effort toward progress against disease through research. 

1 believe that the budget proposal before you will support a sc md 
program which will return rich dividends to the American people and will 
warrant the continued confidence and support of American science. 



Attachment A 
DIVISION OF RESEARCH GRANTS 

INTRODUCTION 

The Research Grants Division of the National Institutes 
of Health was established late in. 19^5 to administer the Research 
Grants program of the Public Health Service. During Fiscal Year 
19^6 research awards totalling $780,158 were ma.de. There has 
been a steady growth of health research during the intervening 
years, as well as greatly increased responsibilities for research 
training. The Division plays an important role in the appropriate 
expenditure of the $125,1+00,000 for research and training grants 
provided the Institutes by Congress for Fiscal Year 1957' 

The Division's responsibility may be broadly and briefly 
described as twofold; to serve as a focal point of coordination 
and administrative assistance for the research and training 
programs of the several Institutes of the National Institutes 
of Health; and to administer a program, of considerable importance 
and increasing size and complexity, in areas of research 
training which do not fall within the categorical functions of 
any of the Institutes. 

This statement is directed particularly at those components 
of the Division of Research Grants ' responsibilities which have 
to do with research and training support in special and general 
areas, either not within or broader than the categorical interest 
of any one Institute. Erief sketches of the overall responsi-. 
bilities of the Division will provide background for better 
understanding . 



These responsibilities are at once broad and complex. 
First, the matter of support of training for research is 
considered. 

RESEARCH FELLOWSHIPS 

These are provided by each of the seven Institutes and 
by the Division. They are all administered by the Division. 
Their purpose : to increase the number of scientists qualified 
to carry on research in the health sciences. 

There are five types of these research fellowships : 

1. Predoctoral - awarded to qualified persons, with 
a bachelor ' s degree or equivalent training, who 
are expected to carry on work oriented toward 
graduate training in the health sciences. 

2. Postdoctoral - awarded to qualified persons with 
an M.D., Ph.D., D.D.S., or other equivalent degree, 
for training in research techniques either in the 
basic sciences or clinical research areas. 

3. Special - awarded to qualified applicants who have 
demonstrated unusual competence for research or 
who require specialized training for a specific 
problem. 

k. Student Part-Time - awarded to acceptable medical, 
dental, nursing, and public health schools in units 
of $600 to provide for part-time research work 
during the school term or for full-time for two 
months at any period when curriculum work is not 
scheduled for the student. A maximum of 8 units 
is awarded to a school. 

5 . Senior - awarded to individuals (a ) to foster 
additional research in the pre -clinical sciences 
(anatomy, physiology, biochemistry, microbiology, 
pharmacology, pathology, biophysics, genetics, 
behavioral sciences), and (b) to support these 
pre -clinical sciences investigators "between the 
completion of postdoctoral training and eligibility 
for permanent academic appointment. 



T S!iie purpose of traineeship awards, which are made "both 
to .Individuals and to institutions, is to increase "both the 
competence and the number of people in fields important to the 
advancement of the attack upon disease which is the concern of 
the Institutes' programs. Traineeships are administered by 
the concerned Institutes- -but the Division of Research Grants 
provides certain central services for them. 

IJIH-PIIS traineeships are provided directly to Individuals 
by several of the Institutes: Cancer, Heart, Arthritis and 
Metabolic Diseases, Mental Health, Neurological Diseases and 
Blindness. They are to ^increase the number of personnel veil 
qualified in health matters, particularly in relation to the 
fields of interest of these Institutes. 

The National Institute of Mental Health provides trainee- 
ships, indirectly to individuals, under training grants awarded 
to institutions for the purpose. 

There are two types of these NIH-Public Health Service 

traineeships: 

1. Regular - awarded to qualified persons having a 
doctoral degree in health fields including related 
biological and behavioral sciences. 



- h 



2. Special - awarded to qualified applicants who either 
possess unusual competence or require specialized 
training for a specific problem, (The National 
Institute of Neurological Diseases and Slindness 
awards only special traineeships to those who 
have completed residency requirements in a specialty, ) 



TRAINING GRANTS 

Grants for undergraduate and for graduate training are 
made to institutions by a number of the seven Institutes, which 
administer these programs with the assistance of the Division 
of Research Grants* central administrative machinery. Also, the 
Division itself administers several special training programs, 
which either involve more than one Institute's interest or are 
directed at trained manpower needs common to the whole field of ' 
medical science and medical practice. 

Undergraduate training grants are awarded by these 
Institutes: Cancer, Heart, and Mental Health, Their specific 
purpose is to establish, expand, improve, or continue instruction 
relating to prevention, diagnosis, and treatment of cancer, 
cardiovascular disease and related gerontological conditions, 
and mental disease. These grants are presently being awarded to 
medical, dental, nursing, and public health schools. 

Graduate training grants are awarded to institutions 
through these Institutes: Cancer, Heart, Arthritis and Metabolic 
Diseases, Dental Research, Mental Health, and Neurological 
Diseases and Blindness. While their purposes vary according 
to the needs of the programs of each Institute, their general 
intent is to increase the level and improve the quality of 
trained manpower in medical, scientific, and related fields. 



- 5 - 
SUMMARY: TRAINEESHIPS AND TRAINING 

The activities in the field of training which are 
administered primarily by the Institutes themselves are reported 
"by the Institutes in connection with their individual appro- 
priations. Later in this statement, however, there will he 
reported those special programs in this field administered 
primarily by the Division of Research Grants. 

GRANTS FOR RESEARCH ITSELF 

The Division of Research Grants is responsible for that 
part of the research grants program not falling within the 
scope of interests of the seven categorical Institutes or of 
common interest to all. In addition, the Division administers 
the grants for construction of health research facilities. 

The Division is particularly charged with providing 
increased emphasis on basic research through research project 
grants. Since the Division is also responsible for analysis 
of the total grant and award programs and for the coordination 
of the administration of all research grants and research fellowships 
programs, the Division is thus in good position to discern gap 
areas and overall needs and to implement and emphasize fundamental 
research in accordance. 

These projects include (l) a significant volume of basic 
medical research not encompassed in the research directly 
pertinent to clinical medicine supported by the appropriations 



- 6 - 
of the various Institutes, and (2) research of many important 
problems relating to medicine which are not of particular 
interest to any Institute. 

Rapid progress in the fight against disease has empha- 
sized the shortage of fundamental knowledge available today. 
Furtherprogress in clinical and applied medical research will 
depend upon an adequate emphasis on basic medical research, 
both that which is readily identifiable as pertinent to the 
study of specific kinds of diseases and that which is even more 
fundamental in nature. The Division of Research Grants will 
support such fundamental studies, with special emphasis on 
biophysics, general physiology, biochemistry, pathology, pharma- 
cology, and toxicology. In the same way that much of the success 
of today's clinical and applied research depends on fundamental 
work of many years ago, the practical application of much of the 
fundamental work of today will not be known for many years to 
come. 

NOT WORTHY PROGRESS 

Progress during Fiscal Year 1957 in promoting and 
coordinating research efforts in the disciplinary areas of 
biophysics and pathology has been noteworthy. 

A fundamental aspect in progress in biophysics is that 
of arousing the interest of qualified mathematicians and physicists, 
as well as of undergraduate and graduate students in these fields, 
to meet the challenge of biological and medical problems. 



- 7 - 
Toward this end, three regional conferences were sponsored by the 
Biophysics and Biophysical Chemistry Study Section of the Division 
to determine the most productive ways of providing training in the 
theory and practice of the complex instruments now used in medical 
research and of developing the needed research in schools of par- 
ticular promise in this field. A comprehensive list of sug- 
gestions has "been provided to the National Advisory Councils to 
encourage these developments and the Study Section is continuing 
to provide a generous part of its individual member's time in 
visiting the laboratories of investigators to assist them with 
their problems in a constructive manner. 

Research in experimental pathology has been similarly 
fostered. The Pathology Study Section established an ad h oc 
Committee on Increasing Research Potential in Pathology which, 
in turn, solicited detailed comments on the needs of the field 
and methods of meeting them from several authoritative sources. 
These comments and suggestions are proving helpful in directing 
attention to areas of research need in pathology, and the 
National Advisory Councils have been apprised of them. 



EXAMPLES OF GENE RAL GRANTS 

Examples of the important problems related to medicine 
supported by general grants include enviromental poisons; 
factors in fertility, reproduction, development and growth; 
and nursing research. 

Environmental poisons have become an increasingly urgent 
problem with the rapid increase in the number of chemical 
compounds to which people are exposed, and a number of studies 
are aimed at securing new information on this problem* 

As one example, the contamination of water supplies 
with chemicals, such as afforded by natural run-off from far^s 
where insecticides have been used extensively, is unrecognized 
and generally of unknown significance, and these and other 
problems of water pollution are to be investigated through 
grant-aided studies. 

Special attention also is being directed toward wasted 
pregnancies (the staggering loss of life from abortions, mis- 
carriages, and premature births) as well as to the physical 
incapacity and mental anguish accompanying congenital mal- 
formations. General grants supported studies related to these 
and other problems of human reproduction, such as causes of 
sterility, tubular pregnancy, and other serious conditions 
which often result in the death of the fetus and sometimes 
the mother . 



- 9 - 

One example of a very important health problem, not of 
primary interest to the objectives of any Institute, is that 
of accident prevention. Accidents rank first among the causes 
of death in the U.S.A. for all ages from 12 months through 3*+ 
years, and rank fourth as an over -all cause of death. One 
research grant on the injury-producing factors in automobile 
accidents is currently being supported and other research in 
the field of accident prevention will be supported by the 
Division. This particular activity is closely coordinated with 
Accident Prevention Activities of the Division of Special 
Health Services., Bureau of State Services. 

In 1956 and 1957; an increased program of nursing re- 
search has been initiated in an effort to improve the utilization 
of nurses and determine better means for recruitment. With 
the constant increase in chronic illness and other problems 
of an aging population, research in nursing will seek to 
evaluate the changing needs for nursing care and promote the 
most effective use of nurses at ail levels of training. 

TRAINING PROGRAMS TO INCREASE MANPOWER 
In addition to the endeavors of the Institutes in this 
direction several special programs are underway to increase 
scientific manpower in additional medical and scientific fields 
related to health. Administered through the Division of Research 
Grants, these include the-: Senior Research Fellowships Program 



- 10 - 

Students Part-time Fellowships , Program for Experiments in Training 
in the Pre-clinical Sciences, and the Epidemiology and Biometry- 
Training Program. 

Brief summaries of the progress made and the activities 
underway in these programs follow. 

SEN IOR RESEARCH FELLOWSHIPS 

The senior research fellowships are distinguished awards 
designed to strengthen the "basic science areas of medical, dental, 
and public health education by fostering research and the develop- 
ment of outstanding academic leaders in such fields as anatomy, 
behavioral sciences, biochemistry, biophysics, genetics, micro- 
biology, pathology, pharmacology, and physiology in the medical 
schools, dental schools, and schools of public health in the United 
States. Unfortunately, these fields are not as strong as they 
should be and research careers are not particularly attractive. 
Furthermore, many of the able investigators in these fields move 
into clinical research, often because of higher pay, with the re- 
sult that fundamental work suffers . 

An essential link in the research training chain therefore 
was forged when the 34th Congress, second session, approved an 
expansion of the I\fIH program of fellowships and training to in- 
clude a category of Senior Research Fellowships. Along with this 
approval was an appropriation of $500,000 with which the program 
could be started during the current fiscal year and an indication 
that the program could be increased gradually to a level of 
o)2,500,000 by the end of five years. This enables the Public 
Health Service to award kO to 50 of these Fellowships annually 



- 11 - 

for a period of five years. At the end of the initial 5 years , 
therefore, from 200 to 250 research fellows will be in advanced 
training in the basic medical sciences. 

The level of salary of the Senior Fellowships is set by the 
institution. These Fellowships are awarded by the Surgeon General 
on the basis of recommendations of a Senior Research Fellowship 
Selection Committee and the National Advisory Health Council which 
consider applicants on a nationwide competitive basis. 

Applications must be sponsored by a basic science department 
of an accredited medical school, dental school, or school of public 
health and must be for persons pursuing careers in one of the 
following sciences: anatomy, physiology, biochemistry, microbiology, 
pharmacology, pathology, biophysics, genetics, biostatistics, and 
behavioral sciences. 

On November 1, 1956 the first Senior Research Fellowship 
awards were made to kk scientists in medical schools, dental schools, 
and schools of public health, who had completed their doctoral 
degrees but did not yet have sufficient research and teaching experi- 
ence to qualify for appointment to higher level of academic positions. 

These five-year senior research fellowships will help to 
stabilize support of highly promising scientists at the crucial 
period of their careers and will make research and teaching in pre- 
clinical departments of nonprofit research and teaching institutions 
much more attractive to individuals who could contribute much to the 
acquiring of new knowledge through basic research. 



- 12 - 

PART-T7JIE FELLOWSHIPS 

The recruitment and orientation of a number of students 
in medical, nursing and public health schools is of utmost 
importance if a trend cf medical education toward research 
orientation is to be fostered. A certain number of physicians 
with research orientation, and an increasing number of full- 
time research workers, must be recruited among those holding 
professional degrees in order to implement clinically the 
research findings in basic fields. No more successful method 
has been found" either to recruit or orient the professional 
student than to allow him. an opportunity to explore the field 
of research during his student days. 

These part-time fellowships have proved most helpful 
to the schools, which apply for them for their students, and 
to the individual students themselves. Often they make the 
difference between a promising student's pursuing medical or 
public health interests, which he and his teachers desire, 
and his having to seek other part-time and summer work, un- 
related to medical interests but which bring enough extra 
dollars to enable him to meet the large costs of professional 
education. In Fiscal Year 1957 , some 817 students in 121 
medical, dental, nursing, and public health schools are 
receiving these part-time fellowships, providing a significant 
aid program. 



- 13 - 

EXPERIMENT AL TRAINING PROHRAM 

For training grants "to improve research and training", 
the Congress appropriated, for Fiscal Year 1957> $500,000 
in the Operating Expenses, National Institutes of Health* 
This program is administered through the Division of Research 
Grants and is expected to make a significant contribution 
because it will provide for experiments in the teaching of 
research and in the improvement of methods of training. 

The funds will permit interested and competent medical 
schools to experiment on the best means to encourage under- 
graduate medical school programs that give promise of pro- 
ductive research training in the university sciences related 
to medicine, 

A national committee, composed of nonfederal scientific 
and medical authorities, has been established to consider 
proposals for implementing these special new experimental 
activities. Indications of interest have been received from 
i number of institutions, looking toward establishing such 
programs. This interest demonstrates, that the funds will be 
significant in meeting an hitherto unmet need. The present 
year's funds will provide for a number of these experimental 
programs to be established, and the $500,000 requested for 
the Fiscal Year 1958 would be used to aid additional medical 
schools to conduct research and training experiments. 



- Ik - 

EPIDEMIOLOGY AND BJEOjgjTR Y TRAINING- P R 033 AM 

The expanding picture of medical research in the United 
States has revealed a number of scientific manpower shortages. 
Among the more crucial of these—and of particular importance 
in the great chronic diseases like cancer , heart disease, and 
mental ills, for example --are the need for trained epidemiologists 
and biometricians. The state of knowledge in these diseases, 
and in others, is today such that if there were an ample supply 
of these skills, it is likely that the conquest of disease could 
be greatly advanced. The design and planning of wide scale field 
evaluations of newer drugs, for illustration, demands these 
kinds of professional people in larger numbers than are presently 
available. For another example, intensive and extensive appli- 
cation of epidemiology- -disease tracing, finding out how, where, 
when, why, and in whom- -in the heart field is cited by all 
authorities as vitally important in progressing against heart 
disease. Thus, the need is well established. 

To help meet it, the National Institutes of Health, 
through the Division of Research Grants, has moved to establish 
a special new program. Late in 1956, an Advisory Committee on 
Epidemiology and Biometry was established. The Committee is 
composed of 11 outside experts, k service representatives, and 
liaison observers from each of the Institutes. The Committee 
has the dual responsibility (l) of reviewing all research grant 
applications involving significant components of either epidemi- 
ological and biometrical procedures and making recommendations 



- 15 - 

to the study sections where initially reviewed, and (2) of 
serving as a training grant selection committee for the establish' 
ment, improvement or expansion of training programs in these 
fields. In connection with the training grant program, funds 
are subscribed from five Institutes having training grant funds 
but without necessary regard to servicing the needs of the 
specific disease categories. 

The strong and widespread interest that attention to this 
problem has evoked from medical and public health schools and 
other institutions throughout the country, and the concerted 
attention of the several Institutes, show that additional 
training programs for epidemiologists and biometricians are 
needed and desired and will be instituted. With sound planning 
through the new Committee and other advisory groups of the 
National Institutes of Health, these new training programs may 
be expected to be of great ultimate benefit. 

SUMMARY 

The Division of Research Grants aids the grants programs 
of the disease -oriented Institutes that comprise the National 
Institutes of Health. The Division also has broad responsi- 
bilities for administration of programs to augment basic 
research and research training. 

Most of current medical advances stem from knowledge 
gained in basic research. The emphasis and encouragement given 
to basic research and to increasing scientific medical research 
manpower through the non-categorical programs of the Division of 



- 16 - 

Research Grants premise much, therefore, for contributing to 
even greater advances in life saving and in renewing medical 
knowledge. The intensifying and integrating of training and 
research achieved through the Institutes' and Division's prograrns 
promise also a shortened time lag between fundamental laboratory 
discoveries and their development into general medical end public 
health practice . The supplementing, stimulating, and coordinat- 
ing role of the Division of Research Grafts is an indispensable 
one in the National Institutes of Health. 



Attachment B 

DIVISION OF BIOLOGICS STANDARDS 

BACKGROUND 
The Federal Government's responsibility for biological 
products for human use began with the passage by the Congress 
on July 1, 1902, of an Act to regulate the sale in interstate 
commerce of viruses, serums, toxins, and analogous products 
applicable to the prevention and cure of diseases of man. 
While some amendments have been made, the statute, now in- 
cluded in the Fublic Health Service Act, is basically the same 
as it was in 1902 when the technical responsibilities of the 
biologies program were assigned to the National Institutes of 
Health, then known as the Hygienic Laboratory. In 1937; the 
Laboratory of Biologies Control was created within the National 
Institutes of Health, and in 19^8, was made a part of the Na- 
tional Microbiological Institute, In June, 1955 > authority was 
granted the Surgeon General by the Secretary of the Department 
of Health, Education, and Welfare to expand the biologies func- 
tion of the Public Health Service with the status of a separate 
division within the National Institutes of Health, to be called 
the Division of Biologies Standards. 

GENERAL MISSION 
The primary function of the Division of Biologies Stan- 
dards is its responsibility for the standards of quality and 
safety of all biological products that come within the 



jurisdiction of the Public Health Service. These include all 
vaccines, antitoxins, therapeutic serums, and human blood in- 
tended for transfusion purposes, as well as products prepared 
from human "blood. 

Because many of these products are derived from living 
organisms, such as "bacteria and viruses, and all, by their 
nature, are potentially dangerous if improperly prepared and 
tested, close surveillance of production and constant improve- 
ment in quality is essential. The development of realistic 
standards for these products and the exercise of proper control 
over them can be effective only if backed by an active research 
program of sufficient flexibility to provide information as it 
is needed for the formulation of such standards. Since the 
creation of the Division of Biologies Standards, the specific 
aim has been the development of an organisation capable of 
first-class work in this important field, based on the concept 
that the control of biologic products should rest on a firm 
foundation of research. 

Through the use of biologic products, such infectious 
diseases as smallpox, diphtheria, ' typhoid, yellow fever, 
tetanus, rabies, and more recently poliomyelitis, can now be 
prevented or treated. Success achieved in this area dees not 
mean that vigilance in control can be lessened or that improve- 
ment of the products should not be pursued. Thus, the Division 
must be alert to possible improvement in production and testing 
of established biological products. 



- 3 - 

In the case of many other infectious and related 
diseases, as for example, influenza, measles, mumps, tubercu- 
losis, hepatitis, and allergies, much remains to he done. It 
is the function of the Division to utilize its resources and 
research potential toward the improvement of products for the 
prevention and treatment of such diseases, and toward the de- 
velopment of better tests for these products. Rapid strides 
are being made in the field of virology, and new vaccines will 
undoubtedly be developed. Experience with poliomyelitis vac- 
cine during the past few years indicates that the evolution of 
such products can be expected to be rapid. 

In addition to its other functions, the Division oper- 
ates the blood bank in the National Institutes of Health Clini- 
cal Center. 

Because of the nature of the products involved, the ac- 
tivities of the Division require a great deal of cooperative 
research with other branches of the Public Health Service, 
members of the biological products industry, state labora- 
tories, the Pan American Sanitary Bureau, and the World Health 
Organization, particularly in the development of international 
biological standards. 

CONTROL PROGRAM 
The provisions of the Public Health Service Act require 
that all products coming within the term "biological products" 
be licensed as a means of ensuring their safety, purity, and 



- k - 

potency. This includes licensing of manufacturing establish- 
ments as well as individual products manufactured. To ful- 
fill these provisions, standards based upon the best scientific 
information available are developed for individual products. 
Members of the Division's staff inspect manufacturing 
establishments prior to licensing and at frequent intervals 
thereafter. Tests for safety, purity, and potency are per- 
formed in the Division's laboratories. Manufacturer's records 
of processing and testing (protocols) are examined. Through- 
out all of these operations staff members confer with appro- 
priate representatives of industry and with scientists in the 
specific fields involved. 

POLIOMYELITIS VACCINE PROGRAM 



Although the activities of the Division during the past 
year concerning poliomyelitis vaccine come within both the 
control program and the research program, the effort expended 
and the general interest in this area call for special mention. 

During this time, close cooperation of the manufacturers 
and the Technical Committee on Poliomyelitis Vaccine with the 
Division continued, making possible the identification of a 
number of technical problems affecting consistent production 
of a safe vaccine and the development of corrective measures. 
This required an extensive testing program, close observation 
of manufacturing processes by members of the staff who made 
frequent visits to the manufacturing plants, and revision of 



the original requirements for manufacturing and testing of the 
vaccine. 

The testing load was particularly heavy during the late 
spring and early summer of 1956. Turing the year, a total of 
151 separate lots of vaccine were submitted by licensed manu- 
facturers for consideration by the Division. This involved 
tests using tissue culture techniques, as well as the inocula- 
tion of monkeys. The expanded resources of the Division during 
1956 made it possible to meet this heavy call promptly, and 
activities during this period permitted the release for use of 
approximately 110 million doses of vaccine. While not all of 
this has been used, it is encouraging to note that no adverse 
reports reflecting on the safety of the vaccine have been re- 
ceived from the field during 1956. 

RES5ARCH PROQRAM 

The importance of a significant basic and developmental 
research program in the operation of effective biologies control 
has been clearly demonstrated during the past year. The Division 
has made considerable progress in this direction, despite diffi- 
culties encountered in the recruitment of qualified personnel 
with the specific backgrounds needed, particularly for the 
higher level positions. Space restrictions have also imposed 
difficulties which cannot be solved until construction of the 
new building to house the activities of the Division is completed. 

During the year, a number of units have been organized and 



- 6 - 

equipped to pursue lines of research related particularly to 
virus vaccines. One such unit is concerned with the study of 
the so-called "orphan viruses" encountered in the course of 
testing vaccine by tissue culture methods. These viruses, 
many previously unidentified, are apparently passed on through 
the tissues from the monkeys used in the preparation of the 
tissue culture media. Their proper identification, a research 
problem, is vital to the interpretation of the results of the 
tests in which these viruses are encountered. 

Another example of the direction of the research pro- 
gram is seen in the establishment of a unit for carrying out 
biophysical and chemic-?.l procedures in the study of biologi- 
cal products. Although primarily concerned with problems re- 
lated to viruses, such as size of particles, filterability, 
and inactivation by chemical and physical means, the facili- 
ties of this unit are nevertheless available when needed for 
studies with other biological products, particularly those 
derived from human blood. 

The lessening demands for testing in connection with 
the release of poliomyelitis vaccine during recent months has 
permitted a reorientation of portions of the testing program 
to meet problems raised by new biological products such as 
adenovirus vaccine, and potentially new products such as 
measles vaccine and live poliomyelitis vaccines, thus strength- 
ening the research programs already under way. 



- 7 - 

Continuing investigations include those pertaining to 
methods of testing for safety, purity, and potency of polio- 
myelitis vaccine; the study of methods of blood collection, 
the equipment used, the testing, and the sterilization of 
blood and products derived from "blood. Research related to 
"blood bank operations and blood transfusion is a particular 
concern of the Division. 

The following avenues of investigation may be cited as 
typical: 

1. Studies relating to methods of determining the 
potency of poliomyelitis vaccine have developed some promis- 
ing leads, stimulating further research in this direction. 
These studies were carried out on a rather extensive scale 
within the Division and also involved cooperation with each 
of the manufacturers licensed for the production of polio- 
myelitis vaccine. As a result of this study, it is now pos- 
sible to design a potency test utilizing the far less expen- 
sive chick as a test animal in place of the monkey. In ad- 
dition, a test of greater precision is being developed which 
will make it possible to study the keeping qualities of polio- 
myelitis vaccine and the relative potency of different lots- 
information which is badly needed but difficult to obtain- - 
using a test based upon monkeys. 

2. Research directed toward increasing the sensi- 
tivity of the testing procedures used for poliomyelitis 



- 8 - 



vaccine "by concentration of vaccine suspensions has met with 
considerable success. 

3« The study of a number of human and other tissue 
culture cell lines is being pursued in an effort to find lines 
which may prove even more sensitive to poliomyelitis virus 
than the monkey kidney cells presently used. Success in xhis 
area, coupled with the work referred to en concentration, could 
thus lead to an even greater margin of safety than is provided 
by present tests. 

k. Work is being started with a view to studying the 
strains proposed for use in live poliomyelitis vaccine. This 
work is directed toward the development of standards which may 
he applied in the event that such vaccines, which are experi- 
mental at the present time, become practical biologic products. 

5. Research relating to development of improved tests 
for safety, purity, and potency of vaccines for the prophylaxis 
of adenovirus infections is being expanded, following the prin- 
ciples which have been successfully applied to poliomyelitis 
vaccine testing. 

6. A long-term study of the complete blood grouping 
and typing of families with heredity abnormalities has been 
initiated in a search for red blood cells of unusual types. 
The unusual cells and sera obtained will be processed and used 
as diagnostic reagents for other tests. The results of this 
study will also serve as an adjunct to work which is being 
prosecuted on the low-temperature preservation of red blood ■ 



- y - 

cells. Red cells can now be stored for as long as 18 months 
prior to transfusion under research conditions, thus making 
available a reserve of blood of unusual types. In present 
blood banking practice, it is possible to store blood for 
only 21 days. 

7. Studies are being initiated on problems of blood 
coagulation in relation to the blood products used for this 
purpose, and further research is being conducted on blood diag- 
nostic reagents, such as those used in determining the Rh factor. 

NEW BIOLOGICAL PRODUCTS 

During the past year, a new virus vaccine has been de- 
veloped to the point where formal standards are required for 
its manufacture. This is the adenovirus vaccine. The Division 
is actively working on problems related to its safety, purity, 
and potency and, aided immeasurably by the experience gained 
with poliomyelitis vaccine, has been in a position to develop 
realistic standards for it. The facility with which this has 
been accomplished is attributable in great part to the expan- 
sion of the staff and resources of the Division, as well as to 
its underlying research program in the field of tissue culture. 

Recent developments with live virus poliomyelitis vaccine 
indicates that this type of immunization may be a possibility 
in the not too distant future. Accordingly, the Divison has 
initiated studies to gain experience in this field, with a 
view to meeting the need for standards should such vaccines 
reach the stage of practical use. 



- 10 - 

Recent developments indicate that active progress in 
the search for a prophylactic agent against measles may be 
successful.. The Division has one unit working on this problem. 

PROGRESS FOR THE I I* WEDIA13 FUTURE 

The Division's program for the immediate future visual- 
izes a consolidation of the strength which has accrued during 
the past year., with increasing emphasis on research in the 
fields of virology and hematology, so as to provide flexibility 
and versatility in meeting new problems, especially those 
raised by new biological products as they emerge from the ex- 
perimental state. 

In addition to strengthening the Division's program, 
the need for adequate physical facilities has been recognized. 
Funds for a new laboratory building to house the Division's 
activities have been made available. It is anticipated, on 
the basis of present estimates, that construction will be com- 
pleted by March 1959 » 

No requests for additional positions are being made, nor 
does the present estimate call for any increases for immediate 
expansion of the program. The estimate reflects, rather, the 
consolidation of program gains provided in 1957^ and the annual- 
ization of the cost of the new staff appointed this year. It 
is expected, however, that at the time of completion of the new 
building, the program will be operating at a level that will 
necessitate some increases. 



OPENING STATEMENT 
Dr. John R. Heller 
Director, National Cancer Institute 
Public Health Service 
before 
COMMITTEE ON APPROPRIATIONS - 19^8 ESTIMATE 
Salaries. Expenses, and Grants, National Cancer Institute 

Summary 

I welcome this opportunity to review for the Committee progress 
in our programs to identify some of the areas which offer particular 
promise. During this year, laboratory and clinical research has been 
expanded in our laboratories and in the universities receiving grants; 
training programs have been expanded to increase the supply of manpower; 
cytology activities have been expanded and centers are being started to 
test the feasibility of using the cell examination technique in cancer 
of the lung and other body sites as veil as cancer of the uterine cervix. 
The cancer chemotherapy program which was so substantially increased 
continues to develop rapidly. 

The appropriation for fiscal year 1957 is $U8,U32,000 or almost 
double that of the prior year, principally for grant and contract 
activities. It early became apparent that it is difficult and in some 
cases undesirable to try to expand research too fast. Scientists in 
universities and medical schools have needed time for preparation, for 
selection of staff in short supply, and for the development of sound 
programs. The problem confronting us this year seemed to be one, not of 
availability of funds but of insuring that these funds were spent wisely. 
All concerned have directed their attention to assure that this was done. 
Study sections reviewing grant applications continued to insist on high 
stando.rds of research, and the National Advisory Cancer Council pledged 



-2- 
itself to approve grants only whore completely warranted and to return 
any funds not so needed to the Treasury. 

During this year, we will just about double our support of 
research through the research grant programs. Our work in establishing 
cytology units has been slow because of the shortage of trained techni- 
cians and difficulty in recruiting personnel at current salary scales. 
We are, however , pleased with the progress that has been made. In the 
chemotherapy program much progress has "been made in screening chemicals , 
in arranging for clinical trials, and in other aspects of the program. 
We are pleased with progress made in securing the cooperation of the 
pharmaceutical industry and in the potential benefits from working with 
them, We have been confronted with the necessity of securing authority 
to negotiate cost-type contracts and with assuring continuity of support 
under contracts. These end related matters of policy should not further 
delay expansion in this area. The new programs in training are all 
under way, and our intramural program is proceeding quite well in care- 
fully selecting key personnel for areas of special interest such as 
virology. 

Current estimates indicate that we will return at least '^>h/l_hk } OQO 
to the Treasury this year. The budget for 1958 calls for an appropriation 
of about $2,o00,000 more than our current years expenditure level. The 
increases are principally to pay grantee institutes a greater proportion 
of the expenses incurred as indirect costs in programs operated with 
grant funds, and to carry some of the programs started during this year 
for a full year in 19 58. 

I should be glad to answer any questions which you may have 
concerning our programs. 



OPENING STATEMENT 

by 

Dr. John R. Heller 
Director, National Cancer Institute 
Public Health Service 
before 
COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
Salaries, Expenses, and Grants, National Cancer Institute 



Mr, Chairman and Members of the Committee: 

I welcome this opportunity to review for the Committee progress 
in our cancer research and related activities and to identify some of 
the areas which offer particular promise in the future. During this 
year, laboratory and clinical research has been expanded in our labor- 
atories and in the universities receiving grants j training programs have 
been expanded to increase the supply of manpower $ cytology activities have 
been expanded and centers are being started to test the feasibility of 
using the cell examination technique in cancer of the lung and other 
body sites as well as cancer of the uterine cervix. The cancer chemo- 
therapy program which was so substantially increased continues to 
develop rapidly. 

These are the programs in which Congressional Committees have ex- 
pressed a special interest, I wish to describe our progress in these 
programs as well as some of the recent developments in cancer research; 
but first I would like to touch briefly on the current financial situa- 
tion. 

The appropriation for fiscal year 1957 is $U8,U32,000 or almost 
double that of the prior year, principally for grant and contract 
activities. It early became apparent that it is difficult and in some 



- 2 - 
cases undesirable to try to expand research too fast. Scientists in 
universities and medical schools have needed time for preparation, for 
selection of staff in short supply, and for the development of sound 
programs. The problem confronting us this year seemed to be one, not 
of availability of funds but of insuring that these funds were spent 
wisely. All concerned have directed their attention to assure that 
this was done. Study sections reviewing grant applications continued 
to insist on high standards of research, and the National Advisory 
Cancer Council pledged itself to approve grants only where completely 
warranted and to return any funds not so needed to the Treasury. 

During this year, we will just about double our support of 
research through the research grant programs. Our work in establishing 
cytology units has bean slow because of the shortage of trained 
technicians and difficulty in recruiting personnel. We are, however, 
pleased with the progress that has been made. The new programs in 
training are all under way, and our intramural program is proceeding 
quite well in carefully selecting key personnel for areas of special 
interest such as virology. 

There is an increase of $2,596,000 in obligations -requested 
in the budget for 195 8. The principal increase of $l,6l6,000 is in 
research grants to pay grantee institutions a greater proportion of 
overhead costs. The direct operations increases total $980,000. 
These increases are for the following: $16,000 for environmental 
cancer studies; $17i+,200 for annualization of positions new in 1957; 
$16,800 for pay in excess of 52-week base; $267,000 for government's 
share of Civil Service Retirement costs and Social Security costs; 
and $506,000 for services performed centrally. 



- 3 - 

I should like now to cover some of our programs in more detail. 

Chemotherapy 

The search for a successful chemical treatment of cancer has 
received much attention "by Congress in the past several years. 
Sparked by the interest and support of Congress, the National Cancer 
Institute has developed a coordinated national program of research 
jointly sponsored by four Federal and two private agencies. An inter- 
agency staff organization -- the Cancer Chemotherapy National Service 
Center -- is now in its second year of operation as the clearing house, 
expediter, and coordinator of hundreds of interrelated research pro- 
jects being carried on throughout the Nation in universities , hospitals, 
government laboratories and private industry. 

These projects in one way or another all aim at the discovery 
of a substance which, like penicillin in bacterial disease, will have 
the property of attacking cancer cells without seriously harming the 
normal cells of the body. There is already abundant evidence that 
several different types of chemical agents, when given by mouth or 
by injection to cancer patients, are capable of causing spectacular, 
though temporary, regression or disappearance of widespread cancer 
lesions. Unfortunately, all of these chemicals have undesirable side- 
effects on normal tissues and most of them are highly toxic to one 
or more types of essential normal cells such as the blood-forming 
cells or the cells which line the intestinal tract. 



- k - 

Thus far the "margin of safety" has been so small that it is 
not possible to destroy all of the cancer cells. The surviving cancer 
cells multiply and eventually kill the patient. It is our hope that 
through intensive efforts we may find chemicals which are much more 
toxic to the cancer cell and much less toxic to normal cells so that 
permanent cures may result. 

The search for better chemicals is largely an empirical program 
of successive steps of "trial and error" screening. For obvious 
reasons , the number of chemicals which can be tested against human 
cancers is quite small. Yet there are literally millions of synthetic 
and natural chemicals to choose from. The chemotherapist must there- 
fore devise a screening system for selecting those few chemicals 
which he may try in man. His constant dilemma is that until he dis- 
covers a cure he has no assurance that the screening method is the 
proper one. 

At present the primary screening is being made mostly with 
transplantable cancers in mice. Substances showing anticancer activity 
in mice are tested for toxicity and pharmacologic properties in other 
animals and when found safe for clinical trial are subsequently 
tested against various types of human cancers. Currently the National 
Cancer Institute is receiving substances from industry in excess of 
25,000 per year for testing in mouse cancer and the demand for test- 
ing continues to increase. Clinical trials are in progress in more 
than 75 hospitals. Meanwhile intensive efforts continue in the search 
for better methods and in basic biochemical research which may provide 






- 5 - 

sufficient knowledge of the chemistry of cancer cells to permit the 
chemotherapist to design a cure on abstract theoretical ground rather 
than by trial and error. 

Two new activities have "been launched daring the year in 
accordancu with Congressional action. Grants have been made to 
training centers for specialized training of research workers in 
suoh shortage areas as clinical research, pharmacology and steroid 
"biology and "biochemistry. An intensive research program in the 
synthesis , assay and clinical trial of steroid hormones in the treat- 
ment of cancer is now under way* 

Although the current year's work has yielded more than a score 
of new agents which have antitumor activity in animals, the most 
significant development from a long range viewpoint has been the 
progress made in securing the interest of the pharmaceutical 
industry. One reflection of this interest has "been the tenfold 
increase in the supply of materials sent in for screening by insti- 
tutions end organizations under contract with the National Cancer 
Institute, 

It would seem, th^n, that many things are going on at the same 
time and at different rates of progress in the field of chemotherapy, and 
everything in obviously more organized and coordinated fashion than hereto 
possible. Some areas of the program are "tooling up" for major screening 
activities. Other areas are already well under way testing, analyzing, and 
evaluating compounds. Industry is being drawn into the picture. Hospitals 



- 6 t 

and medical schools ere pooling resources to study chemotherapy in 
patients. New techniques are being devised and old ones refined. And 
more talented researchers are being given specialized training* Such 
comprehensive and expanded efforts we hope will make major contributions 
to our ultimate objective — the discovery of compounds which will destroy 
tumors with little or no side effects to the patient. 

Cytology 

Chemotherapy involves the search for treatment. Cytology, or the 
study of cells, is concerned with the early discovery of cancer so that 
treatment may be more effective. The cytologic technique involves the 
cell examination by microscope of vaginal secretions secured through a 
quick, simple, painless, and inexpensive procedure. Many members of the 
Committee know of the Memphis cervical cytology project. Approximately 
108,000 women in that ares were examined at least once as of last Fall, 
About 1,^00 biopsies were performed to establish, a final diagnosis, A 
full half of these 1, 500 women were found to have cancer, equally divided 
between early st^ge cervical cancer and advanced uterine c: ncer. Of 
t'.csc with early cervical cancer, fully 90 percent were totally unsuspected; 
and of the advanced cases, about 30 percent were unsuspected. Here is 
continuing proof of the usefulness of this test as a diagnostic aid in 
terms of the medical axiom, the earlier the stege of disease at diagnosis 
the more effective the treatment. 

The Congress encouraged the National Cancer institute to expand work 
in cytology by establishing a number of additional centers. These will 
be in operation this calendar year. Those operated by Institute staff 
people are in Memphis, Tennessee; Louisville, Kentucky; Columbus, Ohio; 
Madison, Wisconsin; San Diego, California J Washington, D, C,; and Houston, 
Texas, The National Cancer Institute is -also making grants for demonstrations 



and investigations of this diagnostic procedure as a useful mass screening 
device. Charlotte, North Carolina; Detroit, Michigan; Kansas City, 
Kansas; and Providence, Rhode Island are screening large population groups. 
These projects are designed to do three things: to explore further the 
actual biological relationship between early cervical cancer and advanced 
invasive uterine cancer; to explore a variety of mass screening methods; 
and to examine the utility of cytologic techniques for other body sites. 

It may be noted that the American Cancer Society has instructed all 
of its field chapters throughout the Nation to urge all women to avail 
themselves of the cytologic test. 

There is good reason to believe that the cytologic technique can 
also be used as a case-finding procedure and an aid to diagnosis of cancer 
involving other parts of the body in both sexes. The problem is one of 
finding an easy method of collecting specimens from the body sites 
involved. The pulmonary system is one in which malignancies have a 
rather high attack rate. The gastrointestinal area is another. These 
areas offer important targets for use of the cytologic examination. We 
are also thinking in terms of the applicability of cytology to the early 
detection of breast, r;.nal, prostate, and bladder cancer. Research in 
these areas is either planned or under way as both direct and grant- supported 
operations in Kansas City, Chicago, and Houston* 

I have mentioned that some of our projects in cytology have been 
delayed due to the difficulty of recruiting and training technicians 
nee led for laboratory work. The Copjdttee may recall previous references 
to an electronic scanner being developed by a major instrument company 
with support of the National Cancer Institute and the American Cancer 
Society. This scanner will be capable of rapidly processing slides and 
separating out the suspicious ones, so that technicians will have fewer 



- 8 - 

slides to examine. The experimental model of this machine is expected to 
be placed in operation at the Memphis project this Fall. Because techni- 
cians will always be needed in the cytology program, training continues 
to be en important aspect. We have enlisted the cooperation of the Office 
of Vocational Rehabilitation through whose regional offices we hope to 
find physically handicapped people who may be quite capable of becoming 
competent technicians. In fact, we have already trained a few of these 
people and placed them in our projects. 

Manpower Train ing 

The National Cancer Institute has been operating a number of 
training programs in various research areas and at different levels. 
Two new programs were instituted this present fiscal year. 

Cancer rose; rch training grants support the training of potential 
investigators in disciplines and techniques pertinent to cancer research. 
This is a new aspect of the training prof ram of the National Cancer 
Institute. It extends and supplements but does not replace the research 
training opportunities available through our regular research fellowships 
and through employment on research projects, Institutions receiving 
funds select and appoint the individuals to be trained and determine the 
stipends to be paid. The Surgeon General has approved 1$ such grants for 
sums totaling just under one million dollars. Slightly more than half of 
the total appropriation for this purpose was allocator- to training in 
fields of chemotherapy and steroid hormones. Such outstanding institutions 
as Columbia, Yale, the Sloan-Kettcring Institute, and Roswell Park Memorial 
Institute are participating in this type of training. General research 
training grants were awarded to the universities of Wisconsin, Minnesota, 
and Kansas j Brown, Stanford, and Washington Universities \ and the Jackson 
Memorial Laboratory and Massachusetts General Hospital, 



- 9 - 

Almost JUOO young scientists will be awarded fellowships fcr advanced 
training in biology, chemistry, physics, medicine, and other fields 
pertinent to cancer research, A recent study indicates that nearly 90 
percent of those trained in this program remain active in research or in 
the teaching of subjects related to cancer, 

Some 133 schools— medical, osteopathic, and dental— will be aided 
by grants to improve the teaching of cancer subjects at the undergraduate 
and graduate levels. This program is considered to be a real factor in 
improving the quality of medical care to be given by the young physicians. 

Clinical traineeships will assist in developing physicians capable 
of more adequately diagnosing and treating cancer patients, About 13>0 to 
160 such grants will be available this year. It is believed that each of 
these physicians serves as a focal point for interesting more medical men 
in the latest cancer diagnostic and therapeutic developments. 

Env ironment al^ Cancer 
Environmental cancer is an area of research in which we are very 
active. For some three years now the National Cancer Institute has been 
studying a group of about 1, 500 uranium miners in the Colorado Plateau 
region. These miners are being followed carefully by physical examinations 
on a periodic basis to determine the extent and nature of occurrence of 
cancer and other diseases. Such a project has at least a three fold purpose: 
first, to study geographic pathology, that is, the occurrence of certain 
diseases in certain areas $ second, to check the occupational hazards 
involved in uranium mining in terms of cancer-causing elements; and third, 
to consider means of developing and maintaining safety devices and features 
in hazardous occupations, in this case, uranium mining. 



tlJ* 






- J-U - 



In a quite different approach, a study continues in New England to 
determine the common denominator environmental factors in the medical 
histories of mothers of normal healthy children, mothers of leukemic 
children, and mothers of children suffering from types of malignancies 
other than leukemia. Analysis of the histories of approximately 200 
mothers has disclosed an almost 2-to-l ratio of clinical allergic response 
(hives, hayfever, and the like) in mothers of leukemic children. This 
observation, though probably inconsequential as of the moment because of 
the small number of cases invelved, suggests an interesting and potentially 
useful approach to the investigation of the effects of a variety of 
environmental factors in the causation of certain types of cancer. This 
study is necessarily slow-moving because of the small number of leukemia 
cases available, but may ultimately yield some very significant information. 

The Institute is cooperating with county health authorities in one 
State to study the impect of a variety of environmental factors upon an 
entire community. It is believed that the distribution of cancer in a 
population should be studied in relation to population density, chemistry 
of the soil, air pollution, background radiation, and other such measurable 
factors. The objective is to determine what common denominators may be 
identified and, if possible what public health control measures might be 
instituted. 

Another aspect of environmental cancer involves research en many 
chemicals and industrial mixtures which are under suspicion as being 
carcinogenic. It is known that cancer does not develop for a considerable 
period following the exposure of a person to a carcinogenic substance. 
Therefore, some of the studies in this area, are, by their nature, long 
range in character and must be sufficiently comprehensive to provide 
numbers of human experiences and exposures adequ/te to furnish significant 
findings. 



- 11 - 

For example, the processing of asbestos, chromium ores, and 
nickel may be associated with cancer of the respiratory tract. A few 
aromatic amines— nitrogen-containing compounds— are included among the 
carcinogenic hazards. Such substances as bots-naphthylamine, U-amino- 
diphcnyl, and benzidine have been related with urinary bladder cancer found 
among workers in factories handling dyes and rubber antioxidants derived 
from coal tar products. The latent period in all these instances average 
about \$ years. With the passage cf time, more and more data of potential 
significance will be accumulated and more precise relationships established, 

Othe r Re search Activities 

In discussing the chemotherapy prog ram, I have mentioned that it is 
but one of many approaches to the stu by of cancer. Chemotherapy grants 
have a wi le spectrum cf coverage ranging from very basic studies to 
testing activities such as grants for screening. Many of the activities 
supporter 1 , under contracts represent the applied research and testing 
approach. 

Such work could not have been started without prior basic research. 
The growth of tumors in mice against which we screen chemicals was possible 
only after long years of basic work. Many of those most interested in 
chemotherapy believe we still need far better screening methods. We may 
not, therefore, have reached the stage of development (such as was true 
in the case of the first atomic bomb) where vie have accumulated the basic 
knowledge which assures the success of an applied research-engineering 
attack. For these reasons, and with Congressional support, we have in the 
past and will continue to invest a substantial proportion of available 
funds in grants and direct research outside the chemotherapy field. 
Work of this type has great promise of finding eventually the solution 
to the cancer problem directly or of providing the knowledge upon which 



tea 



- 1L - 

to launch or modify programs such as the chemotherapy program. Work 
being preformed in these areas is so varied I can only touch on some 
of the most interesting. 

In a significant medical research address, Dr, Wendell Stanley, 
a Nobel Prize winner end until last year a member of the Institute's 
National Advisory Cancer Council, spoke to the Third National Cancer 
Conference in Detroit this past June, This three-day meeting was co-sponsored 
by the Institute and the American Cancer Society, Dr, Stanley stated that 
"the experimental evidence nox-j available is consistent with the idea that 
viruses are the etiological agents of most, if not all, cancer, including 
cancer in man." 

In v±e\j of the similarity of the virus to the cell and the 
consideration of cancer as an abnormality of the individual cell, viruses 
seem to possess potential for serious and intensive investigation in two 
areas, cancer cause and cancer therapy. In the first case, for example, 
it has been fairly firmly established that a certain form of fowl 
leukemia or fowl leukosis has a virus origin. In terms of potential for 
therrpy, the Committee may recall references in prior years to the surprising 
results achieved by a study carried on by a group of scientists representing 
the Cancer Institute and a sister Institute^ Small amounts of so-called 
APC viruses were injected directly into the uterine cervical tumors of 
patients in our Clinical Center who had received other forms of treatment 
for their advanced disease without any affirmative response. In all 
cases, although tumor damage was noticed, the effect of the viruses was 
transitory. The possibility of a potent therapeutic weapon against cancer 
via viruses continues to intrigue our researchers. Working with the 
National Institute of Allergies and Infectious Diseases, research is going 
on with "trained viruses," those frown to live in selected types of tissue. 



- 13 - 

A landmark in the study of the de\ elopment of the human being has 
been achieved by a grantee and his associates in reporting the details of 
the continuous development of the fertilized human egg during the first 
seventeen days of its existence. This is the first time this has been 
done, and the results contribute greatly to our knowledge of the growth 
of the individual. 

In another study, a grantee of the Institute has reported on 
results of the use of vaccines made from the patient's own cancer. About 
30 patients were injected subcutaneously with vaccine, with the aim of 
increasing natural resistance to far-advanced cancer. The vaccine could 
work by stimulating the formation of antibodies against the cancer and 
by increasing the number of healthy defensive cells that resist the spread 
of cancer. Although it is still too early to draw definite conclusions as 
to the effectiveness of this kind of treatment, there was evidence that 
at least one patient developed specific antibodies against her own cancer, 

In still a third study, a grantee has reported on the effects of 
X-irradiation of mice in the presence and absence of the thymus gland. 
The white blood cell cancer of the thymus gland known as lymphoma is 
responsible for lymphatic leukemia in mice which have been subjected to 
whole body X-irradiation. The increased incidence in irradiated animals 
may be prevented by removal of the thymus gland. The grantee now finds 
that implantation of thymus tissue into irradiated mice whose thymuses 
had been previously removed partially restores the inciddnce of tumors, 
These results appear to suggest that an indirect mechanism may be involved 
in tumor induction by radiation, since the thymus grafts had not been 
irradiated. 

Examples of our intramural activities arc equally interesting and 

illustrate the broad spectrum of study which the National Cancer Institute 
program encompasses. 



- Ik - 

We have recently produced in our laboratories a truly synthetic, 
water-soluble, complete diet— a mixture of approximately UO ingredients 
in the form of a white powder. Originally prepared for use in growing rats 
from the weanling stage, this diet has great potential for pro-operative and 
post-operative patients and patients suffering from wasting diseases such 
as cancer, who need food supplied in a form that provides maximum effect- 
iveness with minimum intake, A further potential use of this diet is 
its administration to patients who are denied the use and function of the 
lower part of the gastrointestinal tract, in view of the fact that this 
powder forms an already predigested food. 

In recent months, Institute scientists have witnessed the marked 
regression of a malignant solid tumor fer the first time in several 
patients by chemotherapy. The cancer involved is choriocarcinoma, a 
rare tumor of embryonic origin which occurs in the uterus of women after 
pregnancy and in men as a tumor of the testes, T he drug administered was 
methotrexate, known as an antimetabolite of the vitamin folic acid, 
although we believe this to be an accomplishment of great significance, 
it is based on data obtained from the observation and treatment of a small 
number of cases of a rare kind of cancer Much more work must be done, 
but the potential in this line of investigation is exciting. 

Mycosis fungoides is an uncommon skin lesion generally classified 
with lymphomas and related diseases. Conventional treatment by deep 
X-ray therapy normally exposes large body areas to certain undesirable 
radiation side effects. Recent administration of electrons emitted by 
the Van de Graaff accelerator in our Clinic presents the hopeful prospect 
of more effective treatment of this disease xri.th fewer side effects, 
though the disease was not completely eradicated in the patients treated. 



- 15 - 



Conclusion 

The limitation of time prevents mo from bringing to your attention 
mrny other research areas and investigations and programs, all of which 
show promise of becoming genuinely fruitful contributions to our goal. 
All of the major activities noted today share two attributes : first, they 
could not hrve been expanded to the point of operrtional utility and 
research potential without the great interest of and assistance provided 
by the Congress; and second, they offer more than a glimmer of real 
hope for the discovery and development of mor^ effective — and possibly 
dramatic — means of diagnosing, treating, and preventing cancer, 

I greatly appreciate this opportunity to appear before you and I 
will be delighted to answer any questions or to elaborate on any subject 
of particular interest to the Committee, 



SUMMARY OF 

OPENING STATEMENT 

by 
Director, National Institute of Mental Health 
Public Health Service 

C01MITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Mental Health Activities, Public Health Service" 

Pages 

Progress and new developments have brought important advances 1-2 

in the mental health field during the past year. The sum of 

$35»217,000 is requested to carry on the activities of the 

National Institute of Mental Health during fiscal year 1958* 

Expanded research work in psychopharmacology and the tranquil- 3-6 
izers has been stimulated by the establishment of the 
Psychopharmacology Service Center in the Institute. Increased 
research grants are supporting basic studies of drug action 
and clinical investigations of pharmacologic processes. Similar 
basic work is being conducted in the Institute's own laboratories 
at Bethesda and at the Addiction Research Center. 

The Institute has focused an intensive attack on mental health 6-10 
problems of aging. In addition to broad planning and develop- 
mental work, numerous studies of the biological, psychological, 
and sociological aspects of aging are being supported under 
research grants. A coordinated program of studies on aging is 
also being carried on by the Institute at the Clinical Center. 

Activities in the field of juvenile delinquency include 10 - 12 
continuing work with anti-social, hyperaggressive children. 



- 2 - 

Page s 
Long-term studies on the physical and emotional development 

of infants and children hold promise of vital data that -will 

be invaluable in coping with abnormal behavior patterns. 

Besides supporting research on causes of retardation and 12 - 14 
improved methods of care and treatment of retarded children, 
the Institute is bringing knowledge already available to 
professional personnel who work with the retarded. 

Efforts have been intensified in the following vital areas: 14 - 20 
Drug addiction and basic neuropharmacologic studies; hospital 
management and rehabilitation programs aimed at speeding up 
discharge of mental hospital patients; biochemical studies to 
further understanding of the biological bases of disturbed 
behavior; basic psychiatric research on behavior and person- 
ality development; neurophysiological and neurochemical 
investigations into the structure and function of the brain 
and central nervous system. 

The quality of research applications has improved considerably, 20 - 2? 
and the increased availability of research manpower is reflected 
in the rise in the number of projects submitted for grant 
support. The Institute's program of training mental health 
personnel has been stepped up sharply, new techniqv.es are being 
employed, and striking evidence of the effectiveness of the 
program is already apparent. Community services and biometrics 
programs continue to help build the knowledge, tools, and 
techniques needed for effective control of mental illnesses. 



■ \:yii-> 



OPENING STATEMENT 

by 
Director, National Institute of Mental Health 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Mental Health Activities, Public Health Service" 



Mr, Chairman and Members of the Committee: 

Progress and new developments in many different areas of the 
mental health field have brought important advances during the past 
year. This year has seen the rapid expansion of a program aimed at 
integrating activities in the field of psychopharmacology, the study of 
the effect of chemical substances on mental and nervous processes. 
Significant steps have been taken toward furthering our knowledge and 
developing improved techniques for applying this knowledge in such 
special problem areas as juvenile delinquencjr, drug addiction, mental 
retardation, rehabilitation of mental hospital patients, and the emotional 
disorders of later life. Advances in basic research are bringing us 
closer to the goal of understanding the biochemical as well as neuro- 
physiological mechanisms of the brain and central nervous system. The 
training efforts of the past several years show results in increases in 
the reservoir of trained manpower available to do research, to train new 
mental health personnel, and to provide needed services. The interest 
of the States in developing mental health programs continues to expand, 
and their requests for technical assistance reveal a broader base of 
approach to mental health problems as well as a numerical increase in 
program activities. The quality, quantity, and scope of research 
investigations supported by the National Institute of Mental Health show 



- 2 - 

noteworthy advances. In these and other vital areas the progress that has 
been made and the new steps taken to date show an emerging pattern in which 
each phase of the coordinated attack on mental illness strengthens and 
reinforces other phases, a pattern aimed at gradual encirclement of the 
problem. 

To carry on the work of the National Institute of Mental Health, a 
total of $35,217,000 is requested for fiscal year 1958* Of this amount, 
$27,5^9,000 is for grants and $7,668,000 for direct operations, $16,226,000 
is requested for support of the vitally needed research in the field of 
mental health and mental illness, $10,902,000 of which is for grants in 
support of research projects by non- Government investigators and $5,32^,000 
for the basic laboratory and clinical investigations conducted by the 
Institute itself. In addition, $6*4-7,000 is included in the budget for 
continuation of the research fellowship program designed to help increase 
the reservoir of research manpower in the United States. The sum of 
$12,000,000 is included for training grants to develop the trained mental 
health personnel that are still in short supply and will continue to be so 
for a number of years. For grants to the States for detection, diagnosis, 
and other preventive and control services, the sum of $^,000,000 is 
requested. For professional and technical assistance activities of the 
Institute, $1,273,000 is included in the budget; this will cover, among 
other activities, the work of the Psychopharmacology Service Center, 
assistance given the States in carrying on their mental health programs, 
and consultation on the development of improved methods and facilities for 
the treatment and rehabilitation of mental patients. 



- 3 - 

PSYCHOPHARMACOLOGY AMD THE TRANQUILIZERS 
Psychopharmacology Service Center 

The establishment of a Psychopharmacology Service Center in the 
National Institute of Mental Health has stimulated an expanded program 
of research activity on the tranquilizing and other drugs which affect 
psychological function. This field, which holds much promise for the future, 
is much broader than the tranquilizing agents alone, and embraces all of 
the drugs that act on the central nervous system. Guidance for a program 
in this area was provided in part by a national conference on the evaluation 
of pharmacotherapy in mental illness, sponsored by the National Institute 
of Mental Health in conjunction with the American Psychiatric Association 
and the National Academy of Sciences - National Research Council. Out of 
the deliberations of these experts, including psychiatrists, physiologists, 
pharmacologists and other interested persons, came a statement of research 
problems and needs which highlighted the desirability of pre-clinical studies 
of psychopharmacological agents. There are many gaps in our understanding 
of how these agents act on the brain and how they influence behavior. 
Currently available methods are inadequate and new drug study methods must 
be developed in order to conduct scientifically valid assessments of the 
benefits and limitations of the tranquilizing and other new psychopharma- 
cological agents. 
Supporting Research in Psvchopharmacolopy 

The needed work has begun. There is now increased support of 
research stimulated by the staff of the Psychopharmacology Service Center, 
which also serves as a clearinghouse of information on psychopharmacology 
and provides consultative assistance to investigators. In addition, the 



- 4 - 

Center is working closely with the Veterans Administration which is 
carrying on a large-scale psychopharmacology research program. 

As of January 1, 1957, a total of 1+7 grants on psychopharmacologic 
research were being supported by the Institute, and another 22 appli- 
cations for grants in this field had been received and were awaiting 
Study Section and Advisory Council action. Two mental health career 
investigators are working on long-term studies that are setting patterns 
of research techniques valuable in tranquilizing drug research. Within 
the Institute's own basic and clinical research program 23 separate studies 
are devoted to psychopharmacologic investigations. In all, as of the 
beginning of this calendar 3 r ear, a total of $1,300,000 was being expended 
by the Institute for research in this field. 

Among the investigations being supported by the Institute are 
studies of the basic pharmacological and psychological mechanisms of drug 
action, preclinical screenings of drug efficacy and toxicity, controlled 
clinical studies of the effects of tranquilizers on mental patients, and 
studies of the effects of drugs on behavior, on the central nervous system, 
and on metabolic balance in the body, Radioactively tagged chlorpromasine, 
one of the tranquilizing agents, is being used by one grantee to discover 
the regions of the brain where the drug is distributed and on which it may 
act. Psychological tests of brain-damaged subjects are being compared with 
those of subjects receiving tranquilizers in another attempt to pinpoint 
the locus of drug action. 
Institute Research in Psychonharmacologrv 

One Institute investigator at the Clinical Center is assessing the 
effects of these tranquilizing agents on the course of psychotherapy. Other 
investigators are tracing the metabolism of meprobamate and other neuro- 



- 5 - 

pharmacologic agents in man in an attempt to discover the physiological 
basis for the psychological effects of these drugs. Additional Institute 
investigators are examining the effects of psychopharmacologic agents on 
behavior and performance. 

In still other studies the tranquilizers are being combined with 
other psychopharmacologic agents, such as lysergic acid (LSD), one of the 
psychotomimetic drugs. These are drugs which produce psychosis-like 
symptoms in normal individuals. One Institute scientist is studying the 
effects of various centrally acting drugs on intellectual, motor, and 
perceptual behavior. Similar studies are going on at the Addiction 
Research Center in Lexington, Kentucky, where work done so far has 
demonstrated that reserpine aggravates rather than alleviates the 
psychosis induced by LSD. 

Investigations of the psychotomimetic drugs are continuing in an 
attempt to discover whether biochemical abnormalities are involved in 
mental illness and, if so, what processes are involved. Work is going 
forward on the relation of LSD symptoms to an excess or deficiency of 
serotonin, and on the relations of visual hallucinations to drug effects 
on the lateral geniculate body, a relay station in the visual system in 
the brain. Institute scientists are studying the neurophysiological 
action of these drugs, using intact conscious animals with implanted 
electrodes to correlate electrophysiological effects with changes in 
behavior induced by the drugs. In still another study, using rats of 
various ages, the changes in rate at which the body detoxifies neuro- 
pharmacologic agents are being measured to learn more about the proper 
application of neuropharmacology in treating emotional illnesses of the 
aged. 



- 6 - 
All of these studies and others that are now in process of being 
stimulated by the Psych ophar mac ology Service Center will help to answer 
basic questions about the tranquilizers and other psychopharmacologic 
agents. Much work remains to be done, of course. We do not know, for 
example, whether the improvement in mental hospital patients under drug 
therapy is due solely to the drugs or to what extent it is assisted by the 
more hopeful and therefore encouraging attitude of hospital staff. How 
lasting are the effects of the drugs? Can toxic side effects be eliminated? 
Is there any chemical difference in tissues or cells between schisophrenics 
and normals to account for the wide differences in their reactions to the 
tranquilizers? We need to know more about the probable effects of wide- 
spread use of the tranquilizers with normal individuals— what effect the 
drugs may have on industrial accidents and motor vehicle accidents, and 
whether they will interfere with the ability of children to learn by 
experience. A good beginning has been made by the Center* s staff, however, 
in organizing and mobilizing the research forces for psychopharmacologic 
studies that promise to bring us vital new knowledge. 

KEHTAT HEALTH PROBLEMS OF AGING 
Many of the problems in this field stem from a basic lack of 
knowledge about the psychological and physiological processes of aging and 
about the kinds of preventive and corrective programs needed for older 
people. These processes are fundamental to life itself, and various aspects 
of them are being investigated by several of the National Institutes of 
Health, working singly and together. A Center for Research in Aging has been 
established within the National Institutes of Health to encourage and 
support additional research into the mechanisms of aging. The National 



- 7 - 
Institute of Mental Health is cooperating in the work of this Center, 
To assist in plotting a course for action, this Institute, after careful 
study of the problems, has prepared a program development document entitled 
"Research and Development in Mental Health and the Process of Aging." It 
assesses the present state of the field and indicates necessary future 
developments. Another broad planning effort, being sponsored by the 
Institute jointly with the University of Chicago's Committee on Human 
Development, is a study aimed at discovering why some older people adjust 
to the stresses that come with aging, while others seem unable to do so. 
Findings will enable us to help older people with their problems by 
enlarging our knowledge of the process of aging and of how people meet 
old age successfully. 

Grants-in-aid to the States for mental health programs, and technical 
consultation provided by Institute staff at headquarters and in the 
Departmental regional offices are strengthening State and local activities 
in the field of aging. Although there is increased concern for the aged 
and some States have very active and extensive programs for the aged, these 
advances are not yet widespread and more needs to be done. The State 
mental hospitals provide care for the aged mentally ill, and about half of 
the States have special services such as geriatric wards or buildings in 
their mental hospitals. However, relatively few persons aged 65 and over 
are served by mental health clinics, although some are undertaking active 
preventive and rehabilitation programs to keep non-psychotic aged persons 
out of mental hospitals. 
Studies of Aging 

Numerous studies of the biological, psychological, and sociological 
aspects of aging are being conducted by investigators assisted by research 



- 8 - 
grants from the Institute. As of the end of 1956, Ik separate projects 
in this field were being supported for a total of about $300,000. Among 
them, biological studies are attempting to assess the normal and patho- 
logical effects of aging on the nervous system. One investigator is 
making a comparative analysis of cerebral blood flow in normal and 
psychotic aged persons. Others are studying electroencephalographic 
changes in age, and the role of heredity in mental health or mental 
disease in later life. 

Psychologists are seeking accurate measures of the differential 
decline that comes with age of such functions and abilities as perception 
and learning. This type of knowledge is essential for effective planning 
of services for the aged. Many other such psychological studies are needed, 
and are discussed in "Psychological Aspects of Aging", published in 1956, 
which is the report of a research conference on aging sponsored and 
supported by the Institute in 1955. 

Sociological studies on aging supported by research grants include 
investigation of the problems that arise when retired persons migrate from 
their homes to other parts of the country. The whole problem of what 
retirement from work means in terms of changes in family living is also 
under study. Other workers are evaluating the relative effectiveness of 
inpatient and outpatient psychiatric rehabilitation of older persons. In 
the same general area, the collection and analysis, by the Institute's 
Biometrics staff, of basic data on mental hospitalization of the elderly 
are providing valuable guidelines for further investigation. The rapid 
increase of first admissions of persons aged 65 and over to State mental 
hospitals in the past two decades, from 156.6 per 100,000 civilian 
population in 1933 to 203.6 in 1950, raises important questions to which 



- 9 - 
we must seek answers: Are more older people becoming mentally ill or is 
there better diagnosis of mental illness? Is there greater acceptance of 
hospitalization for mental illness or are there fewer other facilities for 
caring for the aged? Another biometrics investigation has revealed that 
rates of release of elderly patients from mental hospitals have remained 
constant during the past four decades. Does this mean that the prognosis 
for senile dementia will remain poor, that the various therapies used are 
unsuccessful, that custodial care is as effective as active therapy, or 
that the hospital is the only facility available to meet the needs of these 
older people? 
A Coordinated Research Effort 

In the meantime, intensive anatomical, biochemical, physiological, 
and psychological studies of aging are being conducted by Institute 
scientists at Bethesda. The Institute's Section on Aging is conducting 
an integrated research program on aging of the nervous system, covering 
a wide range of biological and social science studies and using both 
human and animal experimentation. Studies range from electron microscopy 
of cellular constituents to observation of human behavior in the aged. 
Among significant recent findings by this group of scientists is that the 
slowing of responses with increased age is primarily a property of the 
central nervous system. In addition, investigators in the Section on Aging 
are studying age changes in perception and motor responses, and are engaged 
in basic biochemical studies of cellular energy production and protein 
synthesis. 

Another broad research undertaking in the field of aging is the 
Institute's interdisciplinary study of mental health in the elderly. A 



- 10 - 

group of healthy elderly men, who have volunteered for a study at the 
Clinical Center, are being given more than ^0 separate examinations by 
psychiatrists, psychologists, social scientists, biochemists, neuro- 
physiologists , internists, and many other specialists. Age changes in 
cerebral metabolism and blood flow are being studied by Institute 
neurophysiologists, and an intensive psychiatric assessment of these 
aged subjects is being made with psychiatrists as interviewers and 
observers. A comprehensive profile of normal age changes, uncomplicated 
by the common diseases of old age, is thus being assembled, which can be 
used as a yardstick to assess abnormal mental, physical and social changes. 
Data already collected indicate correlations between altered self-per- 
ception and declining physical condition and the presence of depressions 
in older people. 

Besides these activities, the Institute makes available a wide 
variety of information and educational materials on the subject of aging, 
and participates actively in Departmental programs in this field. Institute 
staff assisted in the planning and conduct of the Federal-State Conference 
on Aging, held in June 1956, at which a comprehensive statement of needs 
and plans was developed. 

JUVENILE DELINQUENCY 

In addition to basic research on child development, which many 
scientists feel holds the best answers to the major social problem of 
juvenile delinquency, the Institute is supporting and sponsoring a great 
deal of applied research in this field. 

As of the end of 1956, there were 16 grants for delinquency studies 
and the total amount of grant support in this area was $350,000. One 



- 11 - 

investigator is studying the efficacy of special school curricula for 
delinquents. Another is making a long-term analysis of children classified 
as psychopathic personalities. Still another is examining aggressive 
behavior patterns of delinquent streetcorner gangs. 

A broad study of community, interpersonal and personality factors 
jn juvenile delinquency, supported by the Institute, is being conducted 
by a Midwestern research center with unusual skills and experience in 
conducting social research. Also with Institute support, the head of a 
famous East Coast child guidance clinic is doing a pilot study of 
families of anti-social children. Still another project is combining 
investigation with delinquency prevention, using mental health resources 
to deal with and reduce the incidence of juvenile delinquency while 
learning more about the problem. 

In the Institute's own research program, work with anti-social, 
hyperaggressive children continues. Extensive data are being compiled on 
the establishment of therapeutic relations with these children who 
commonly resist all attempts to form close relationships. Investigators 
in the Child Research Branch are analyzing learning disturbances and 
studying the use of effective teaching programs as part of therapy. In 
this same general area, a survey of reading disability is being conducted 
by the Institute's Mental Health Study Center in Prince Georges County, 
Maryland, as the first step in a major study of the relation between faulty 
reading skills and childhood behavior disorders or later maladjustments. 
These and other long-term studies which are described below under the 
heading of child development hold great promise for enlarging our basic 
knowledge and providing a scientific framework within which, hopefully, we 
can cope with juvenile delinquency more successfully. 



- 12 - 

CHILD DEVELOPMENT 
Within the Institute's own research program a long-term study on 
the physical and emotional development of infants and children is now 
well underway. We are seeking to determine the factors in early infancy 
and childhood, among them family relationships and parental attitudes 
and practices, which lead to adjusted or maladjusted behavior in later 
life. Another goal of these studies is to differentiate between the 
roles that heredity and early environmental influences play in producing 
maladjustment. We are trying, for example, to determine whether behavior 
difficulties are produced by faulty parental attitudes, or whether diffi- 
culties arise because the parents are unable to cope with unusual problems 
presented by the child. 

In addition to these investigations, the Institute is supporting 
major research in this field through its grants program. One grant is 
for an extended interdisciplinary study on child development, combining 
physiological, psychological, and sociological approaches. We expect 
to get vital baseline data from this study that will help to establish 
norms for various phases of child development. Another grant- supported 
project is for a longitudinal study on the ways different children 
develop to cope with life's difficulties. Increased knowledge of how and 
why children develop different patterns of behavior is essential for full 
understanding of deviant, anti-social behavior, and the development of 
effective corrective action. 

MENTAL RETARDATT OM 
During the past fiscal year the Institute has continued to expand 
its program of planning, research, and training activities in the field of 



- 13 - 
mental retardation. Altogether it is expected that approximately 
$1,200,000 will be expended in this area during fiscal year 1957. 

A search for leads related to the etiology of mental retardation, 
being conducted by the National Association for Retarded Children with 
partial support from the Institute, is serving collaterally to develop 
widespread interest in work on this subject. The American Association 
of Mental Deficiency, which is the professional society in this field, is 
developing guidelines, under a grant awarded by the Institute in 1956, 
for research, training of personnel, and program planning. 

In addition to this developmental work, the Institute is supporting 
a total of 18 research studies on causes of retardation, and on improved 
methods of treatment and care for retarded children; eight new grants on 
retardation were made during calendar year 1956. One investigator being 
assisted by an Institute grant is studying the use of phenylalanine- free 
diet for children afflicted with a metabolic disorder which results in 
mental deficiency. Another investigator is developing more accurate 
diagnostic tools for differentiating retardation from other childhood 
disorders. A third is devising methods for more accurate assessment of 
psychological capacities, such as perception, reasoning and memory, in 
retarded children. Other researchers are working on genetic and hereditary 
aspects of retardation, and on metabolic aspects of the problem. 

Through its training grants, the Institute is bringing the new 
knowledge we already have about effective care and treatment to pediatricians, 
psychiatrists, clinical psychologists, social workers, and others who work 
with the mentally retarded. In addition, the mental health professional 
consultants on the Instituted staff and in the Department's regional 



- 11* - 

offices are providing increased assistance to States and local communities 
that are carrying on services for the mentally retarded. It is expected 
that this heightened activity will further be stimulated by the grants to 
State training schools for the mentally retarded under The Health Amend- 
ments Act of 1956. 

DRUG ADDICTION 

The most extensive program of research on drug addiction is the 
one carried out by the Institute itself, particularly at the Addiction 
Research Center in Lexington, Kentucky. There is, however, increasing 
interest in the subject by outside investigators, evidenced by more 
applications for grant-supported research on drug addiction. The 
Institute has, as part of its program planning and development work, 
acted to stimulate such interest. The Instituted consultant on drug 
addiction participated in a special international study of drug addiction 
for the World Health Organisation. Surveys of facilities for care and 
treatment of addicts were made for three large cities on the East Coast 
and in the Midwest. In addition, the Institute is conducting negotiations 
to set up a demonstration project aimed at utilizing effective and 
economical procedures for post- institutional care of drug addicts. 

At the Addiction Research Center, the past year has brought much 
progress. Fourteen new analgesics were tested for addictive properties 
as part of the Center's continuing responsibility for protecting the 
public against uncontrolled clinical use of potentially addicting 
substances. Eleven of these new analgesics proved to have some degree 
of addiction liability. In the meantime, the Center continues its search 
for synthetic drugs to replace morphine and related agents, the goals 



- 15 - 

being to provide a secure domestic supply and eventually to find a non- 
addicting analgesic. 

Studies on intoxication caused by barbiturates, alcohol, and 
other drugs such as the psj^chotomimetics and the tranquilizers are 
uncovering promising new research leads. Because there is some evidence 
that continued use of meprobamate may produce physical dependence on the 
drug, the Center is planning clinical and animal studies on this substance. 
The Center is conducting experiments with other related substances in the 
hope of shedding light on how they act in the body and thus gaining some 
insight into the etiology of psychoses. 

Biochemical, neurophysiological, neuropharmacological, and ps\'"cho- 
logical investigations are slowly building our basic understanding of the 
mechanisms of drug addiction. These studies range from the effects of 
chronic drug intoxication on the cellular chemistry of the nervous system 
to the relationship between personality characteristics and proneness to 
addiction. 

A major contribution during the year, made by the Institute scientist 
in charge of the Drug Addiction Center* s neuropharmacological studies, was 
the preparation of a comprehensive review on "The Relation of Psychiatry 
To Pharmacology," probably the most definitive analysis of the literature 
in the field that has been made to date. 

SPEEDING DISCHARGE OF MENTAL HOSPITAL PATIENTS 
The rehabilitation of mental hospital patients, with particular 
emphasis on the effects of hospital staffing and ward administration, has 
continued to be a major concern of the Institute. A significant report 
on the "Socio-Environmental Aspects of Patient Treatment in Mental Hospitals ,« 



- 16 - 
embodying the results of a research conference sponsored by the Institute 
late in 1955, is now in preparation. The charting of the areas for 
needed study will help to integrate and direct such work. 

Within the Instituted own research program, pioneering work on 
the study of the mental hospital as a social system is going forward. 
Psychiatrists and social scientists are investigating the ways in which 
patients adapt to the hospital and the contributions to therapy made by 
various staffing arrangements. One such study is exploring the avenues 
to the creation of an effective therapeutic environment through various 
nursing techniques. Other clinical studies, being pursued with adult 
schizophrenic patients as well as with disturbed, hyperaggressive children, 
are concerned with techniques of intervening when patients exhibit gross 
signs of behavior disorder. 

A number of Institute research grants have gone to support studies 
on hospital staff and administration, and their effect on patient care 
and rehabilitation. In addition, the Institute's Hospital Consultation 
Service staff has drafted guidelines for policies and procedures to 
implement mental health project grants in this general area that will be 
made possible under Title V of Public Law 911 (8^th Congress). 

BIOCHFMTCAL AND P SYCHIATR IC RESEARCH 
The past year has witnessed an intensification of basic biochemical 
and psjrchiatric research activities, in the light of mounting evidence 
that disturbed metabolism may be involved in some types of mental disorder* 

In the Institute* s laboratories, basic studies are being conducted 
on amino acid metabolism > and on transmethylation, a mechanism for conversion 
of drugs in the body. Detailed knowledge of where and how the psychotomimetics 



- 17 - 

and other psychopharmacologic agents act in the body will add to our 
knowledge of the relation of central nervous system structures and 
processes to psychological functioning. Such knowledge is the pre- 
requisite to an understanding of the biological bases of behavior in 
general and disturbed behavior in particular. Still other studies are 
focussed on the action of drugs and hormones at the cellular level in 
man and in experimental animals; this basic research is concentrated on 
those drugs that simulate or alleviate mental illness. New biochemical 
tools, refined methods for physiological measurements, and the use of 
tranquilizing and hallucinogenic drugs as experimental variables are 
spurring concerted efforts by Institute scientists and research grantees 
to correlate physiological and metabolic processes with observable data 
about normal and disturbed behavior. 

The unique facilities of the Clinical Center at Bethesda have 
enabled the Institute to engage in a large program of such broad-based 
and multidisciplined research into mental illness. Correlated studies 
of the psychiatric, psychological, biological, and pharmacological aspects 
of mental illness are supplementing investigations into improved treat- 
ment methods for schizophrenia and other psychoses. Institute investigators 
also are conducting basic research to develop theoretical frameworks for 
understanding normal behavior and personality development. Psychosocial 
studies are being aimed at increasing our understanding of the psycho- 
logical and social determinants of behavior, and give promise of basic 
knowledge parallel to the knowledge we seek about biological bases of 
behavior. Mental illnesses, as disorders in behavior, need to be under- 
stood in terms of all the elements that comprise and influence behavior. 



- 18 - 

Psychiatric studies at the Clinical Center, employing both experimental 
animals and humans of all ages, are utilizing contributions from psychiatry, 
internal medicine, various branches of psychology, sociology and anthro- 
pology, physiology, biochemistry, and pharmacology. 

In a unique group of studies on the dynamic forces within the 
families of mentally ill patients, the Instituted Child Research and 
Adult Psychiatry Branches are studying the families of hyperaggressive 
children and of adult schizophrenics. Some parents are receiving 
individual or group psychotherapy; others are living with their schizo- 
phrenic child. Extensive studies of families are being conducted in 
connection with the Institute's child development work; physiological 
and biochemical studies are being made of parents and their schizophrenic 
children who are patients at the Clinical Center; and the Laboratory of 
Socio-Environmental Studies has carried out several studies of the families 
of schizophrenic patients, in the community and at St. Elizabeths Hospital. 
These investigations have uncovered important new data about the effect of 
family relations and attitudes on the response of the patient to treatment, 
and his reintegration into the family and the community. 

OTHER BASIC RESEARC H 
Fundamental studies on the structure, function, and metabolism of 
the nervous system in health and in disease are going forward at the 
Institute and in research laboratories throughout the country. Already 
promising results are beginning to appear. As an example, a number of 
neurophysiologists, working independently of one another, have arrived at 
a remarkable conclusion about the mechanism of neural impulse. Hitherto, 
it had been supposed that nerve cells worked on an "all-or-none" basis: 



- 19 - 

given a sufficient stimulus, a uniform impulse was transmitted; if the 
stimulus was insufficient, no impulse was transmitted. It has now been 
ascertained that there are graded response mechanisms at both ends of the 
nerve cell - at the neuron receptor endings and dendrites and at the axon 
terminations - which permit the accumulation of a variety of weak stimuli 
that later lead to impulse transmission when the threshold is reached. 
This mechanism allows for graded "neuronal responses - and allows neuronal 
junctions to perform complex integrations. This discovery helps to explain 
a great many complicated cerebral activities which could not be accounted 
for by previous theories. 

Important pioneering research in neurochemistry is also going 
forward in the Institute's laboratories. Our investigators have recently 
determined the structure of a synthetic analogue of ribonucleic acid which 
gives important information concerning the structure of this naturally 
occurring substance, believed to be a template for the manufacture of 
highly complex protein molecules so vital to growth, function, and 
repair of the nervous system. By analyzing behavior mechanisms in a variety 
of experimental animals in relation to local brain stimulation or 
destruction, id.th or without drug intervention it has been possible to learn 
more about the functions of the brain, in health and in disease. Utilizing 
special techniques for the measurement of circulation and oxygen consumption 
in the human brain, investigators are studying the effects of anxiety and 
of a number of psychopharmacologic agents on brain metabolism. Preliminary 
findings indicate that anxiety is associated with an increased energy 
utilization by the brain. 



- 20 - 

SUPPORT OF RESEARCH 

During the past few years, there has been an increase in the 
number of trained mental health research workers. Besides, research 
scientists of many different disciplines have become more interested in 
mental health research. These increases are reflected in the increased 
quantity grant applications for support of meritorious research projects. 

The number of research applications received during the second 
quarter of fiscal year 1957 reached an unprecedented high. The number of 
applications considered at the November meeting of the National Advisory 
Mental Health Council was 100 percent greater than for comparable periods 
during the past 2 years. Investigators of proven competence are proposing 
program research on a broader, long-term basis, and institutions not 
previously represented among Institute grantees are proposing worthwhile 
studies. As investigators acquire more skill in mental health research, 
and as methodology and research design in this field become perfected, a 
higher proportion of applications received will be able to pass the 
requirements for grants , 
New Trends 

The trend in grants awarded during the past year has been toward 
larger amounts and longer periods of support. During fiscal year 1957, 
37^ grants will have been supported at an average of $19,000 per grant. 
In addition, approximately 20 large-scale grants in excess of $20,000 are 
being supported for studies in psychopharmacology, aging, and other special 
areas. This development is consonant with the advice of research 
strategists that the wisest investment is in large-scale, long-term, stable 
support to able investigators who are allowed freedom to follow the most 
promising leads. 



- 21 - 

Another new program, originated by the National Institute of 
Mental Health, is the awarding of small grants (under $2,000) to support 
pilot or exploratory studies and promising young investigators, and to 
stimulate research interest in small institutions. Indications are that 
this program is filling a definite need. Some 125 small grant requests 
in the field of mental health have been received, and about 60 percent 
of these have been approved. 

Other significant trends in grant- supported projects are the 
increased emphasis on biologically and physiologically oriented research 
in mental illness, and the broadening base of scientific research 
disciplines involved in mental health research. These trends are being 
strengthened by the Institute's Career Investigator Program which pro- 
vides psychiatrists and scientists of other disciplines an opportunity to 
acquire training in disciplines other than their own. 

INCREASING THE RESERVOIR OF TRAINED MANPOWER 
The Institute's program of training to produce the vitally needed 
mental health personnel was stepped up sharply during the past year. The 
amount expended for teaching grants was almost doubled over vfhat it had 
been during fiscal year 1956, At present, 2*4-1 schools are receiving 
support for mental health training programs. The number of schools 
receiving support for instruction in graduate psychiatry and clinical 
psychology increased considerably, and the amount of the grants for 
instruction in all of the mental health professions has been raised so 
that more training can be supplied. 

The number of trainees jumped from 863 to 1,872 this year, an 
increase of 116 percent. The amount of the stipends was increased to 



- 22 - 
attract more able young persons to this field. 

The Institute's career teacher program, designed to develop a 
reservoir of educators to train in the mental health disciplines, is now 
supporting the development of 28 such specialized individuals, a 75 
percent increase over last year. The demand for such educators will 
continue to increase as new mental health programs are developed. 
Research Manpower 

Our program of assisting in the effort to increase manpower to 
keep pace with the increased range of mental health research has likewise 
expanded. This year we will be supporting an estimated 180 research 
fellows. The fellowships, x^hich encourage research in various scientific 
specialties and in critical areas of mental health need, have already paid 
off in terms of available manpower. A great majority of former fellows 
are now in full or part-time research; 20 percent are now recipients of 
research grants or are on the National Institutes of Health research 
staff. It is encouraging to note, also, that there has been a sharp 
increase in the demand for research fellowships this year, indicating 
increased interest in mental health research on the part of promising 
young scientists. 
Mew Trends in Training 

A number of important trends in the Institute's training activities 
should be noted. One is the inception of a training program in the basic 
sciences such as neurochemistry, neurophysiology, and psychopharmacology, 
which are becoming more and more important in mental health research. 
Another trend is toward the training of workers to provide services in 
especially critical areas, such as aging, retardation, delinquency, 
alcoholism and childhood psychoses. 



!/. : t . 



- 23 - 

In the support of undergraduate psychiatric training in the 
medical schools, the tendency is toward the development of preclinical 
departments of medical psychology as a means of giving the medical 
student more information about the society in which his future patients 
live and in which he will be treating them. At present, grants of about 
$23,000 each are made to 36 medical training centers. 

The National Advisory Mental Health Council has recommended that 
psychiatric education in nursing schools be placed on the same basis as 
in medical schools. The psychiatric education of the nurse is about k0 
years behind that of the medical student, and the need is for psychiatric 
education integrated with obstetric, medical, surgical and public health 
training of the nurse. Of the 1^1 collegiate or 4-year schools of 
nursing, it is estimated that about 80 are ready to develop a program 
on psychiatric aspects of nursing. The Institute is providing grants, 
in amounts up to $15,000, to kO of these collegiate schools of nursing. 

Special pilot projects and evaluation studies are being conducted 
to assess present training methods and to develop new ways of incorporating 
the latest research findings into the training of mental health personnel. 
Small grants to universities and State mental health programs are enabling 
practicing mental health workers to receive up-to-date information about 
rehabilitation of the mentally ill, care and training of mentally retarded 
children, prevention of juvenile delinquency, and similar important fields. 
In addition, basic concepts from the behavioral sciences are being incorpo- 
rated into the training of key professional people, such as lawyers, 
ministers and teachers, who deal with important aspects of human behavior. 
Training Pavs Off 

Letters written to the Institute by recipients of traineeships and 



- 21* - 

training grants attest to the great need that these grants are filling* 
Trainee after trainee has told us. that without support provided by- 
Congress he or she could not have entered one of the mental health 
disciplines, and all express satisfaction with their choice of career. 

An unsolicited letter from the head of one department of 
psychiatry of a large-city medical school illustrates the benefits that 
training programs and entire communities can derive from the Institute's 
training grants. In this case, the medical school's department of 
psychiatry set up a full teaching and training program in the psychiatric 
division of the city's general hospital. In addition to providing 
training for medical students and residents in inpatient psychiatry, the 
program offers significantly improved services to the patients. Because 
the general hospital is now able to provide short-term psychiatric treat- 
ment, the admissions to the local, publicly supported mental hospital 
have decreased sharply, with an estimated saving to the taxpayers of at 
least $200,000 in one year. The medical school feels that this whole 
program could not have been possible without the gradual development of 
its department of psychiatry, aided by Institute grants over a period of 
7 years. News such as this is a sign that we are proceeding along lines 
that are productive and that will, eventual^, help create the reservoir 
of mental health manpower needed to cope with the problems of mental 
illness and related disorders. 

COMM UNITY SERVICE ACTIVITIES 

The increase in funds available for grants to States for community 

mental health programs has made it possible to increase the minimum Federal 

allotment from $19,000 to $25,000. Eighteen States receive this mimimum. 



- 25 - 
The States themselves have, in the meantime, been increasing their own 
expenditures for these purposes and, in some cases, are expanding their 
efforts into training and research as trail as service programs. To date, 
however, 23 States are attempting to operate mental health programs on 
funds totalling less than $50,000 per year, which is the amount estimated 
to be required for a small State staff or one average-sized mental health 
center . 

Nevertheless, there is widespread improvement in the coverage and 
quality of State and local mental health programs. More clinics have been 
established, and preventive programs involving education of and consultation 
to non-psychiatric agencies have been instituted. Special mental health 
services in connection with aging, mental retardation, alcoholism, juvenile 
delinquency and other problem areas are being given increased attention. 
As of the end of fiscal year 1956, Federal funds accounted for only 12 
percent of the $26 million budgeted by the States for community mental 
health services. Current State plans indicate an increase to $28 million 
for fiscal year 1957. 

Federal grant money is being used to excellent advantage for all 
types of community mental health services. In addition, the amount 
budgeted by the States for training has increased to more than $700,000 
this fiscal year, an increase of almost 100 percent in the past 2 years. 

The Institute's staff of professional community mental health 
consultants has been expanded to meet the increasing demands for assistance 
from the States. During 1956, technical assistance projects were added to 
the Institute's techniques for supplying this assistance. These projects, 
which utilize conferences to present new knowledge and improved methods, 
are designed to help the States move into frontier areas. Six such projects 



«"'•',.- 



- 26 - 

were completed, covering such areas as after-care of mental patients, 
organization and administration of State mental health programs, and 
public school approaches to the problems of emotionally disturbed children. 
In addition to these projects, the Institute is initiating field demon- 
strations to illustrate successful ways of providing services in connection 
with mental health education, drug addiction, and post-hospital services 
for mental patients. 

The Institute's Hospital Consultation Service staff surveyed the 
need for mental health facilities in Alaska, provided consultation to a 
number of State hospitals, and surveyed the facilities for the mentally 
retarded of one State on request of the Governor. Guidelines for evaluating 
community mental health programs are being set up by the Institute's 
professional staff in this area, and assistance T\ras provided to a wide 
range of regional, national, and international organizations operating in 
areas pertinent to mental health concerns. At the Institute's Mental 
Health Study Center in Prince Georges County, Maryland, community mental 
health studies are continuing on reading disability as a symptom of actual 
or incipient emotional disorder, and on types of community services needed 
by former mental hospital patients. 

BIOMET RICS RESEARCH 
During the year, one additional State joined the Model Reporting 
Area, which has as its objective the provision of data on mental hospital 
populations that will make meaningful comparisons possible. The 18 States 
now cooperating in this project care for about two-thirds of the patients 
resident in State mental hospitals in the United States. In addition, 8 
of these States are contributing analytical data on specific groups of 
patients, following their first admission to a mental hospital. 



- 27 - 

The Institute is sponsoring a special study, by one of the out- 
standing schools of public health in the country, of the admission 
patterns of an entire State mental hospital system over a period of 50 
years, from 1900 to 1950. This study will provide information that will 
enable us to correlate data on movement in and out of hospitals with infor- 
mation on outcome of treatment. Another study sponsored by the Institute 
will provide data on patients admitted to a State hospital over a period 
of J-K) years. The objective here is to relate patient movement in and out 
of the hospital with social and environmental factors. 

There is similar expansion in the Institute's activities in the 
collection and analysis of data on persons treated in outpatient psychiatric 
facilities. The Direc t ory of Outpatient Psychiatric Clinics , published last 
year in cooperation with the National Association for Mental Health, compiles 
information received from 95 percent of the 1,23^ clinics in the Nation. 
The Institute's Biometrics staff has also provided the States with consul- 
tation on methods and techniques for collection of data about recipients 
of psychiatric aid. 

SUMMARY 
Altogether, the prospect for the future in mental health is 
beginning to be more hopeful. The inception of new programs and the steady 
advances on almost all fronts are building up a store of knowledge and an 
armamentarium of tools and personnel which should lead to effective pre- 
vention, treatment, and control of mental illnesses. 



SUMMARY OF OPENING STATEMENT 
by 
Director, National Heart Institute, Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Salaries, Expenses, and Grants, National Heart Institute, Public Health Service" 

Mr. Chairman and Members of the Committee: 

Mortality from heart disease — a cost of over 825,000 U.S. lives last 
year—assumes igajor proportions for both sexes after age 45, but is much higher 
for men. Between 1935 and 1955, the death rate for women in the ages 45-64 
has dropped 18%; the rate for men has jumped 20%. Arteriosclerosis and hyper- 
tension account for more than 90% of heart disease deaths. 

The Heart Institute's program, keyed to provisions of the Heart Act, is 
a four-faceted approach to the heart disease problem. These facets are: 

Conduct of Research . Institute research is aimed at bettering under- 
standing' of cardiovascular diseases and improving methods of prevention and 
treatment. In atherosclerosis, studies are progressing on the role of fatty 
substances and on drugs to block cholesterol formation in the body. In hyper- 
tension, the search for useful drugs continues, as does study of brain centers 
which control blood pressure. Studies in heart failure are helping to define 
the chain of events leading to edema. Developments in surgery include a new 
cathcrization technique and a procedure that abolishes abnormal heart rhythms 
occurring in hypothermia. Epidemiological findings show that risk of developing 
coronary disease is increased by hypertension, high cholesterol count, or overweight 

Support of Researc h. Cardiovascular investigations throughout the 
country were increased and accelerated in fiscal 1957. By following recommenda- 
tions of the Heart Council for stimulating research potential without jeopard- 
izing the high standards previously maintained, about $8,400,000 of new 



- 2 - 
applications of high quality had been awarded by December 31 as compared with 
$2,500,000 for the similar period last year. Examples of progress reported were 
completion of the cooperative study on lipoproteins, improvement of drug treat- 
ment in hypertension, successful transplantation of the kidney in humans, new 
information an bacterial action in rheumatic fever, and development of new tech- 
niques for open heart surgery. An important forward step was initiation of a 
large-scale study for a much needed clinical evaluation of cardiovascular drugs. 

Support of Training , Research training grants and fellowships are 
providing training opportunities for young scientists and advanced training for 
established scientists. Clinical training grants and traineeships are assisting 
the training of future medical teachers, physicians, nurses, and others in the 
heart disease field. The bulk of the expansion in fiscal 1957 has been in research 
training grants at the graduate level. As of January 1, 1956, 20 such grants 
amounting to $269,526 had been awarded, whereas on the same date in 1957, 37 
totaling $989,662 had faeen made. These grants were made in nine areas of 
established need. 

Development of Community Programs . Increased funds for grants to States 
have stimulated expansion of control activities and have strengthened programs at 
the State and local level. Examples include establishing new clinics and diag- 
nostic centers, initiating epidemiological studies, and addition of professional 
personnel to State staffs. Increased funds for technical services — consultation 
and professional assistance rendered to States--are being used for a new activity, 
the assignment of medical officers to States or local areas te give impetus to their 
heart programs. This has already resulted in studies, activities, and programs 
within the States which otherwise could not have been started. 

Expansion of the Heart Institute program in 1957 (including establishment of 
a Center for Aging Research) has accelerated progress and is leading to greater 
future gains against cardiovascular diseases. 



OPENING STATEMENT 
by 
Director, National Heart Institute, Public Health Service 

COMMITTEE ON APPROPRIATIONS 

1953 ESTIMATE 

for 

"Salaries, Expenses, and Grants, National Heart Institute, 

Public Health Service" 

Mr. Chairman and Members of the Committee: 

H EART DISEASE: FACTS AND TREND S 

The National Heart Institute program, planned to carry out the pro- 
visions of the National Heart Act passed unanimously by the Congress in 
1948, is a four-faceted approach to the heart disease problem. This problem, 
comprised of some 20 cardiovascular disorders which make up the general 
category of "heart disease", costs the Nation, extensive death, disability, 
suffering, and economic loss. In 1956, it took upwards of 825,000 lives. 

Heart disease hits hardest at the older ages, but nonetheless 29 
percent of deaths from this cause occur at ages under 65. Even in the 
relatively young age group 25-44, heart disease is the leading cause of 
death and after age 45, mortality from this cause assumes major proportions. 
This is true for both men and women, but in the age group 45 to 64 the 
rate is much higher for men and they usually develop a much more severe 
heart disease than do women. This fact is of particular significance 
since men at these ages are in their most productive years and still have 
heavy family and community responsibilities. Between 1935 and 1955, the 
heart disease death rate for women in this age group has decreased 18 
percent; the death rate for men, however , has jumped 25 percent during 
the 20-year period. 

The impact of heart disease on the people of this country is largely 
attributable to arteriosclerosis and hypertension. Some heart diseases of 



- 2 - 
former numerical significance have dwindled in importance as causes of 
death to "minor" classifications. Also, rheumatic fever and rheumatic 
heart disease, now preventable, show a steadily declining mortality 
trend. But hardening of the arteries and high blood pressure, which lead 
to heart attacks, strokes, and other serious consequences, together now 
account for some 90 percent of heart disease deaths. 

In the case of hypertension, it is encouraging to note that the 
slight but perceptible downward trend, which was reported last year in the 
age groups 45-74 for three causes of death which have hypertension as an 
important etiological factor, continued through 1955. With regard to 
arteriosclerosis, death rates from this cause such as coronary heart 
disease continue to increase. 

The four facets of the National Heart Institute approach to the 
heart disease problem are the conduct of research within the Institute, 
the support of research in research centers throughout the country, nation- 
wide support of training related to the cardiovascular diseases, and 
assistance in development of community control programs. These activities 
are elements for achieving its continuing objectives: to find new and 
better ways of preventing, treating, and curing heart disease and to assist 
the full application of what is known. The funds appropriated by the 
Congress for the 1957 fiscal year have enabled sound and progressive 
development of Institute activities toward these ends. 

HEART INSTITUTE R ESEARCH 

The intramural research program conducted by the National Heart 
Institute is directed toward the betterment of our understanding of the 
causes and nature of diseases of the heart and blood vessels and the 
improvement of methods of prevention and alleviation. Studies range from 



- 3 - 
basic organic chemistry and biophysics to clinical medicine and surgery, 
and apply the skills of many disciplines, A substantial part of the pro- 
gram is geared to take advantage of opportunities to apply available tech- 
niques to immediate problems. Examples are such areas as the screening and 
trial of new drugs in hypertension and atherosclerosis and in the improve- 
ment of surgical diagnostic and therapeutic procedures. 

At the same time, progress in such applied research can continue 
only so long as there is new scientific information to apply. This is why 
the well-rounded program of the Heart Institute gives adequate stress to, 
and depends heavily upon, the acquisition of new knowledge by research in 
the fundamental sciences directly pertinent to medicine and the prompt 
interchange of such information with those more immediately concerned with 
human disease. Studies in fundamental biophysics, biochemistry and physi- 
ology therefore constitute a major part of Heart Institute research. 

Some of the areas receiving emphasis in the Institute's intramural 
research program are given below. 

Atherosclerosis 

Atherosclerosis (the common, serious form of hardening of the 
arteries) is a disease of the large and medium-sized arteries characterized 
by the deposition of fatty materials in the vessel walls. These deposits 
may enlarge till they completely block the artery. More often, the 
atherosclerotic plaque becomes rough and ulcerated and blood clotting 
(thrombosis) occurs on its surface, cutting off the flow of blood. Such 
atherosclerosis and thrombosis can and frequently do occur in almost every 
part of the body. The most serious problems occur, however, when the 
affected arteries supply vital tissues such as the heart muscle itself 
(coronary arteries) or the brain (cerebral arteries). Through its 



- 4 - 
predilection for these areas, atherosclerosis has become the most frequent 
cause of death in the United States. 
Role of fatty substances : 

It is nov/ well established that atherosclerosis is frequently asso- 
ciated with excesses of certain fatty substances in the blood. In large 
populations it has been shown that on the average the higher the intake of 
fat the more likely the occurrence of coronary heart disease. In the 
individual, on the other hand, deviations in the handling of fatty substances 
by the body are more easily identified as associated with those compli- 
cations of atherosclerosis which make possible the diagnosis. The working 
premise on which much of our research effort is based is that the best 
prospect for prevention of atherosclerosis lies in the fuller understanding 
of how fats are normally formed or broken down in the body; the identifica- 
tion of processes which are disturbed in association with atherosclerosis; 
and the interposition of drugs, diets, and sach other measures as might 
favorably influence fat metabolism. 

l?hen the association of atherosclerosis with disturbances of fat 
metabolism aroused new interest in the latter subject, very little was 
known about it. The Institute's research program has made an appreciable 
contribution to the progress in this field. Fats absorbed from the 
intestine are transported to the tissues in the form of large molecular 
aggregates of fat and protein. In the tissues a lipoprotein lipase 
("clearing factor" system) is responsible for remo\al of the fat and its 
deposition in the tissues, and for the later breakdown of tissue fats to 
supply the needs of the body for fuel. The various components of this lipo- 
protein lipase system have been identified and their significance is under 
study. 



- 5 - 

The isolation of a strain of bacteria able to destroy the anti- 
clotting drug, heparin, has made it possible to show that heparin or a 
very closely related substance is an integral part of the clearing enzyme 
system. Studies are continuing in the hope of identifying, for the first 
time, the chemical structure of heparin and obtaining information con- 
cerning its source and disposition in the body. Meanwhile it has been 
shown that the unjoined fatty acids released from the body's fat depots 
by the action of a specific enzyme constitute a major resource in meeting 
the caloric requirements of tissues. Studies have shown that the utili- 
zation of these fatty acids is very rapid indeed. The regulation of 
their release and uptake is under study since it has been found that when 
there is interference with this process, large fatty aggregates of the 
type most often associated with atherosclerosis make their appearance in 
the blood. 

Studies are continuing along another line in attempts to prevent 
atherosclerosis by lowering the blood concentration of the fatty substance 
cholesterol. Accomplishment of this through dietary restriction has been 
only mildly successful because the body uses other foodstuffs to produce 
a rapid formation of cholesterol within the body. Current efforts are 
aimed at preventing this internal formation through the administration 
of inhibitory drugs. One such drug, delta-4-cholestenone, is currently 
under study but work has not yet progressed to the point of establishing 
whether or not it has therapeutic or preventive value. Meanwhile the 
search for other inhibitors is continuing. 

Hypertension 

Hypertension or high blood pressure ranks next to atherosclerosis 
as a cause of heart disease. The initiating causes of most types of 



- 6 - 
hypertension remain unknown and \tfhile attempts to identify the underlying 
abnormalities continue, efforts are also directed at relief of the 
disease by administration of drugs that reduce blood pressure. A number 
of such drugs are available and their value in severe cases has been 
demonstrated. However, undesirable side effects and difficulties in 
management of dosage have limited the use of these drugs. While several 
drugs developed in the Heart Institute screening and testing program have 
not proven useful in the human disease, this field remains a fertile one 
for further therapeutic advances. 

Progress in study of the chemistry of brain centers which control 
blood pressure and other automatic body functions has continued. The 
theory has been proposed that the opposing stimulation and moderating 
functions are mediated by centers controlled by different chemical sub- 
stances, known respectively as serotonin and norepinephrine, and that 
drugs act on these centers by causing the release of or preventing the 
action of these substances. This has suggested new ways to approach the 
central control of blood pressure through effects on these substances*, and 
the mechanisms by which serotonin and norepinephrine are produced, stored, 
and released are under intensive investigation in Heart Institute labora- 
tories, and have assumed new importance. 

A new factor fortuitously discovered to be present in the plasma 

of patients with hypertension, but not of normals or patients with other 

diseases, has led to the initiation of studies to determine its nature 

and significance. This material was recognized through its capacity to 

modify the contraction of the isolated heart. 

Congestive Heart Failure 
Congestive heart failure is a complex group of physiologic dis- 
turbances which characterize inability of the heart muscle to carry the 



- 7 - 
load imposed upon it. It is a common result of many forms of chronic 
heart disease. Further progress has been made in studies aimed at 
defining the chain of events which lead from failure of the heart muscle 
to perform its work adequately to the retention in the body of excesses 
of salt and water which lead to the formation of edema (dropsy). Whereas 
there has been strong inferential evidence that the last link in the 
chain is excessive secretion of certain hormones by the adrenal glands, 
this has recently been shown directly by the collection of blood directly 
from the adrenal veins in dogs with congestive heart failure. 

Research in the application of drugs to increase the excretion of 
salt and water has continued; several complex substances which might be 
direct chemical antagonists of the adrenal salt-retention hormone were 
tested and found to be ineffective. Studies are currently being carried 
out on a promising new diuretic (drug causing increased salt and water 
excretion) . 

A substance present in normal blood and having an effect on heart 
muscle contraction similar to that of digitalis has been under study for 
several years. Within the past year the material has finally been iso- 
lated in pure form and its chemical nature has been worked out. 

Surgical Approaches to Heart _ Disease 

While some forms of heart disease (notably rheumatic) are pre- 
ventable, there will probably remain a significant incidence of congenital 
abnormalities and other anatomic lesions best approached by surgical 
repair. At the present time, the latter as well as the end results of 
rheumatic fever and some atherosclerotic damage to large blood vessels 
are often best handled by surgical means. Continued improvements in 
surgical diagnostic and operative technique are making possible wider 



- 8 - 
application of heart surgery, and are decreasing risk and improving 
results in those disorders in which it has become standard treatment. 

Catheterization of the left side of the heart, by a technique 
developed in the Heart Institute, has proven to be a safe procedure and 
extremely valuable in the diagnosis of several types of lesions, in selec- 
ting patieiitts for surgery, and in evaluating surgical results. The more 
well-known method of heart catheterization (the Nobel prize in medicine 
was recently awarded to the three men, two of whom are Heart Institute 
grantees, who introduced it into medical research and practice) does not 
reach the left heart chambers because the lungs are interposed between 
right and left heart. The left heart is reached, in the new procedure, 
by direct puncture through a bronchoscope. 

With this technique it is possible to measure the gradients of 
pressure across valves suspected of deformity and thus to evaluate the 
extent of disease, and postoperatively, the adequacy of the corrective 
measure. Also, new procedures have been devised which make it possible 
to determine accurately the location of abnormal connections between 
heart chambers and to evaluate the functioning of heart valves. 

The application of hypothermia (body cooling to around 86-07 F) , 
in order that interruptions of the circulation can be made for longer 
periods (6-8 minutes) without damage to the brain, has now become a safe 
procedure. Resistant abnormalities of the heart rhythm have been 
virtually abolished by a procedure devised in Heart Institute laboratories. 

Studies in the application of pump-oxygenators (artificial heart- 
lung machines) to permit more extensive open-heart surgery with more pro- 
longed interruption of the circulation continue to make progress and its 
more widespread use in clinical surgery is to be anticipated. 



- 9 - 
Framingham Epidemiology Stud y 

The Heart Institute's epidemiological research being conducted 
at Framingham, Massachusetts, is concerned with studying a randomly- 
selected cross-section of the adults of this community over a long 
period of time to find out how many people have heart disease, when it 
develops, and what factors appear to be associated with it. 

Preliminary findings on the first four years of the study indi- 
cate that men aged 45-62 with any two of these three conditions --hyper- 
tension, overweight, high serum cholesterol--are about nine times as 
likely to develop coronary heart disease as men with none of these con- 
ditions. Considered separately, hypertension shows the greatest associ- 
ation, with men with high blood pressure developing coronary disease 
four times as frequently as those with normal pressure. Men who were 
greatly overweight were found to develop coronary disease three times 
as often as those of normal weight, and this same risk appeared to exist 
for men with a high serum cholesterol count when compared with those 
who had a normal cholesterol level. In the coming year, the relation 
of nutritional factors to the development of heart disease will be 
octensively explored. 

SUPPORT OF RESEARCH AN D TRAINING 

The research grant and training programs of the National Heart 
Institute provide part of the means through which the resources and 
ingenuity of the scientific community are directed against heart disease. 
Through research grants, funds are provided to accelerate the research 
productivity of established laboratories, to assist in the development of 
new laboratories, to encourage the introduction of new skills and new 
ideas into cardiovascular research, and to help coordinate the attack 



■,'■[ 



- 10 - 
against these diseases. Research training grant and research fellowship 
programs provide funds for the development of training opportunities for 
young research scientists and for the advanced training of already estab- 
lished scientists. Clinical training grant and traineeship programs 
provide assistance for the training of future medical teachers and of 
physicians, purses, and public health workers in the cardiovascular and 
related areas. Thus the National Heart Institute training and research 
grant programs constitute a means by which persons can be recruited and 
trained to cope adequately with research problems and by which new ideas 
can be developed, thoroughly investigated, and then translated into 
effective tools for the prevention and treatment of heart and blood vessel 
diseases. 

G rants for Heart Research 
The National Advisory Heart Council held a special meeting in July 
of 1956 to advise the Heart Institute on the extension and development 
of the research grant program in light of the increase in funds provided 
by the Congress for fiscal year 1957. The Council felt that with the 
additional funds the Heart Institute was in a favorable position to 
actively explore the research potential in cardiovascular disease in the 
country and to stimulate utilisation of this potential in fiscal 1957 with- 
out relaxing the high standards that had been maintained in the past. The 
Council 1) recommended a plan of action for the coming year for explora- 
tion of this research potential, 2) established guiding principles for 
stimulating research in this potential without jeopardising the high 
standards acceptable to the Study Sections and the Council, and 3) pro- 
posed the development of additional opportunities for training in connec- 
tion with research grant projects as a means of further research develop- 
ment. 



- 11 - 

The recommendations have been followed with gratifying results. 
Two of the three Council meetings awarding funds from fiscal year 1957 have 
now been held, and approximately $8,400,000 of new applications of high 
quality have been awarded. This compares with $2,500,000 of new applica- 
tions awarded during the similar period of last year. The confidence which 
the Congress has shown through providing increased funds for this program 
has resulted in sound expansion of cardiovascular research, and has per- 
mitted an orderly and constructive program development. 

Diseases which are receiving particular emphasis are arteriosclerosis, 
hypertension, congenital heart disease, cerebral vascular disease, rheu- 
matic fever, and chronic pulmonary disease. Disorders of circulation (e.g., 
congestive heart failure :nd shock) and studies of aging as a biologic 
process are also being given special attention. 

The Heart Institute research grant program over the past nine 
years, and in particular over the past three years, has given us some of 
the answers to the critical problems of saving lives, The fact remains, 
however, that for the most part we do not know why these diseases occur, 
how they can be prevented and, in many cases, how they can be diagnosed 
early enough to prevent irreparable damage. Concurrent with program 
activities related to the immediate treatment of patients, the Institute 
is continuing to develop its program aimed at the prevention of these 
diseases and the early diagnosis and complete rehabilitation of those 
afflicted with them. This long-range program is dependent upon uncovering 
the causes of these diseases and of perfecting methods for preventing 
their occurrence. 



- 12 - 

A number of research developments have been made during the past 
year in investigations supported through the research grant program. A 
few examples of these follow. 

Studies in Arteriosclerosis 

This year marked the completion and publication of a cooperative 
research study supported by the Heart Institute since 1950 and carried on 
by research teams at the Cleveland Clinic, the University of California at 
Berkeley, the University of Pittsburgh and Harvard University. This project 
provided information on the relationship of cholesterol and lipoprotein 
(fat-protein) levels in the blood to the appearance of cardiovascular 
disease in previously well persons. The study, involving 15,000 subjects 
of which about 5,000 males were intensively studied, has led to a national 
and international re-evaluation of these measurements as indicators of 
the probable development of myocardial infarction. These results will 
have an influence on the kinds of further research on the etiology and 
diagnosis of arteriosclerosis. An example of the by-products of this 
cooperative study is the determination, by investigators at the University 
of Pittsburgh, that a specific group of lipoproteins similar to and 
probably identical with the serum lipoproteins, is present in substantial 
amounts in atherosclerotic plaques in the aorta, the body's main artery. 
This group of lipoproteins, designated as Sf 12-100, could not be demon- 
strated in those blood vessels in which no plaques were observed. 

The influence of dietary factors on the production of athero- 
sclerosis and high serum cholesterol continues to be intensively investi- 
gated. An important study conducted at the University of Minnesota has 
recently been published. In this investigation, carefully controlled 
high and low cholesterol diets were compared in groups of older and 



- 13 - 
younger men in the United States and in two groups of men on the Island 
of Sardinia, where the type of diet differs considerably from the usual 
diet of the United States. The results, in all groups, appear to indicate 
that the cholesterol content of the blood is essentially independent of 
cholesterol intake in the diet. Research in this area by other investi- 
gators indicates that the level of cholesterol and lipoproteins in the 
blood varies considerably from one individual to another and may be 
related to age, sex, dietary fat, functioning of the liver, and endocrine 
glands such as the thyroid and the adrenals. 

While investigation continues on the causes, development and diag- 
nosis of arteriosclerosis and on the diseases which result from this 
abnormal thickening of arterial walls, a surgical technique, endarterec- 
tomy, has been employed at the University of California at Los Angeles 
and the University of Minnesota in the treatment of arteries which have 
become completely blocked by the atherosclerotic lesions. This tech- 
nique involves the removal of the diseased portion of the lining of the 
artery so that the flow of blood can be resumed through the vessel and 
new normal tissue can grow into the affected region to replace the athero- 
sclerotic plaque. Operations of this type have been performed success- 
fully in a few cases on arteries in the legs and on the coronary arteries 
supplying the heart muscle. 

Studies in Hypertension 

Recent research at the Schools of Medicine at Boston University, 
Georgetown University and the University of Tennessee has evaluated the 
use of several hypotensive drugs, either alone or in combination, and has 
determined more specifically the relationship of their action to heart, 
blood vessel and kidney function. This has led to techniques which 



- 14 - 
increase their effectiveness and minimize the undesirable side effects 
of prolonged administration. 

Hypertension often is associated with kidney disease. One of the 
most outstanding achievements in the treatment of hypertension associated 
with renal disease has been the successful transplantation of an entire 
kidney from one individual to another. This operation was performed suc- 
cessfully for the first time by a group of doctors from the medical and 
surgical services of the Peter Bent Brigham Hospital and Harvard Medical 
School in Boston, Repeated attempts by many investigators to effect the 
transplantation of tissues and organs from one individual to another have 
been almost entirely unsuccessful because of incompatibility between the 
tissues of host and graft. The grafted tissue is treated like a foreign 
substance and is destroyed before it can become established in its new 
location. The kidney transplants which have been accomplished in two sets 
of identical twins mark an important milestone in the field of tissue and 
organ grafting, as well as in the therapy of hypertension and kidney 
disease. 

Rheumatic Fever Res earch 

Rheumatic fever and the heart damage which may follow rheumatic 
fever have been traced to infections with a specific type of bacterium, 
the group A hemolytic streptococcus. The manner in which streptococcal 
infections bring about these cardiac changes still remains obscure, and 
investigations are underway in a number of institutions to determine the 
mechanism of bacterial action. At the Children's Hospital in Philadelphia 
and at Stanford University School of Medicine, methods have been estab- 
lished for the isolation and identification of the antigens produced by 
the bacteria and for the study of their physical and chemical properties. 



., ! .' -n I ' 



- 15 - 
This should lead to exact knowledge of these substances and of the anti- 
bodies which react with them. 

Among the various products elaborated by the group A streptococci, 
two are known to have an effect on the heart. Research conducted at the 
New York Hospital-Cornell Medical Center and the New York University 
College of Medicine has shown that one of these products, crystalline 
streptococcal proteinase, may bring about destruction of heart muscle. 
The other substance, streptolysin 0, reduces the oxygen consumption of 
heart muscle, thereby causing a reduction in the amplitude of its contrac- 
tion. Such fundamental studies are increasing our knowledge of the origin 
of rheumatic fever and rheumatic heart disease. 

One of the later effects of rheumatic heart disease is the damage 
which occurs to the heart valves. Relief of this condition by open heart 
surgery, employing a pump -oxygenator to substitute for the heart and lungs, 
is being successfully carried out at the University of Minnesota Medical 
School and at other research laboratories. M^re recently just a mechanical 
pump and a technique whereby the patient's own lung serves as the oxygen- 
ator has been used. 

******* 

During fiscal year 1958 the Heart Institute anticipates supporting 
additional research in these and many other areas. In arteriosclerosis 
improved methods of diagnosis will be sought after, as well as more infor- 
mation about the dietary and environmental factors that affect this 
disease; in hypertension the search for better drugs will be continued and 
those already available will be further assessed; in congenital heart 
disease preventive methods will be stressed as well as the development and 
perfection of improved methods of treatment. 



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- 16 - 

The year will also see continuing development of fundamental in- 
formation about the structure and function of the heart and blood vessels 
and the factors that affect them. This development is to be facilitated 
through encouragement of research in pre-clinical areas and in basic bio- 
logical research related to medical programs. 

The Institute's research grant program is geared to meet research 
needs in the cardiovascular field not only through support of independent 
investigators at universities and medical schools, but through stimu- 
lating collaborative efforts by a number of research teams where large 
scale investigation could establish the significance of research findings. 
Such planned research carried out by voluntary cooperation of several 
laboratories may determine rapidly what otherwise might take a very long 
time to resolve conclusively. 

Evaluation of Cardiovascular Drugs 

Research has developed many new drugs useful in treatment of heart 
and blood vessel diseases. Because of their number and diversity, there 
is great need at the present time for evaluation of drug therapy, particu- 
larly in the management of hypertension. The need will be met. A grant 
has been made to the American Hospital Association for a period of five 
years to carry on a nation-wide program for evaluating the effectiveness 
of drugs in the treatment of cardiovascular diseases. This grant repre- 
sents a significant step in the struggle to alleviate high blood pressure 
and other crippling disorders and in promoting better health of the nation. 

As envisioned by the Research Director of the Association, a 
cooperative study of wide scope will be conducted, using well -designed and 
adequately controlled testing methods, with participation by research teams 
in hospitals and research laboratories. In addition to establishing 



K...- 






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:.«vJU»'{ V. 



- 17 - 
reliable criteria for use of drugs, a further result of the study will 
be improved methods for evaluation of drugs. 

Training Grants and Awards 
Training Grant Program 

The training grant program of the National Heart Institute has as 
its goal providing additional research scientists, teachers, and highly 
skilled physicians for the immediate and long-term battle against heart 
and blood vessel diseases. The program provides training opportunities 
for specially selected persons in research and clinical areas of docu- 
mented need. Through direct and indirect traineeship awards young people 
preparing for careers in research, academic medicine and public health 
are being assisted in obtaining the necessary training for future posi- 
tions in research, teaching, and community service. 

Graduate Training Grants . Clinical training grants at the graduate 
level provide for the development of special training facilities for 
physicians, nurses, and public health workers, particularly where these 
persons are preparing for careers in teaching and community service* 
Through these grants the medical school teacher and the community health 
leader of the future are being trained. Research training grants at the 
graduate level are being made to universities, medical schools, hospitals, 
and other selected institutions, for development and improvement of 
research training programs in the scientific disciplines basic to cardio- 
vascular research. 

The bulk of the expansion of the training grant program in fiscal 
year 1957 was in research training grants at the graduate level. Growth 
in this program is reflected by the fact that for the fiscal year 1956, 
20 of these grants amounting to $269,526 were awarded, whereas in fiscal 



"•; : ;:.!''. 



- 18 - 
1957, with two of the three Council meetings which award grants from 
1957 funds having now been held, 37 totaling $989,662 have been awarded. 
Grants were made in the areas of aging, anatomy, biophysics, biostatistics, 
enzymology, pathology, endocrinology, physiology and surgery. Particular 
consideration was given to those areas of need which were carefully docu- 
mented by groups such as the Advisory Councils and Study Sections who 
are especially well-qualified to provide such evaluations. For example, 
two areas of training need which were established have been in biostatistics 
and research pathology. That these needs are now being partially met is 
reflected in the fact that three years ago there were no training grants 
in biostatistics and now there are eleven, and two years ago there were 
none in research pathology and now there are ten active grants. 

By providing funds on a laboratory, departmental, inter- 
departmental and inter-institutional basis, the training of persons in the 
many skills necessary for modern research is being done. As part of a 
graduate training grant, funds are provided for traineeships enabling 
the institution to recruit and encourage the most capable young people 
to enter upon long programs of training for careers in medical research. 
In fiscal year 1958 the National Heart Institute proposes to continue 
emphasizing the graduate research training grant program to assist In the 
development of the medical scientist of the future. Special attention 
will be given to development of programs in areas such as nutrition, 
aging, pharmacology, genetics, and epidemiology. 

Undergraduate Training Grants . Awarded to schools of medicine, 
osteopathy, and public health, these grants assist the training of young 
physicians and public health workers in the modern methods of diagnosis 
and therapy of cardiovascular disease. Such training equips the clinician 



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- 19 - 
with the skills necessary to provide his community with techniques and 
abilities that previously were available only in highly specialized 
medical centers, 

Traineeships . This program offers physicians, nurses, and public 
health workers the opportunity to acquire advanced cardiovascular training 
in preparation for academic careers in clinical research, teaching, and 
community service. It has provided funds by which about 100 outstanding 
young physicians, nurses, and public health workers prepare themselves 
each year for teaching appointments in training institutions of the 
nation, and for careers in health agencies. It is anticipated this program 
will continue at about the same level next year. 
Research Fellowship Program 

The research fellowship program provides an important means by 
which young scientists are recruited into the cardiovascular and related 
research areas and are trained for careers as medical scientists. Attempts 
are made to encourage research interests early in the careers of capable 
young persons and to assist mature investigators in obtaining additional 
highly specialized research experience. 

Traditional undergraduate training in the medical school does not 
ordinarily prepare young physicians for careers in medical research. The 
part-time fellowship program provides an opportunity for selected medical 
students to obtain research experience early in their professional careers. 
Given substantial initial support in 1956 and 1957, these awards are 
expanding the pool of medical research manpower. 

Predoctoral and postdoctoral research fellowships provide young 
scientists and physicians the training preparatory to careers in cardio- 
vascular research. In the preclinical sciences special emphasis has been 



in 



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- 20 - 
given to the training of scientists in the areas of pathology, pharma- 
cology, genetics, biophysics, and epidemiology. In clinical research, 
emphasis has been given to preparing young people for research careers 
in the areas of arteriosclerosis and hypertension. Through special 
research fellowship awards, the more advanced scientist is assisted in 
improving his skills through highly specialized training. 

Working closely with national scientific societies and with volun- 
tary health agencies, the National Heart Institute through its research 
fellowship program plans to continue in fiscal 1958 to provide the leader- 
ship necessary to recruit and encourage young people for careers in 
cardiovascular research, 

COMMUNITY PROGRAM DEVEL OPMENT 

Grants to the States and Territories are made according to a formula 
based on population and economic need to encourage and promote the develop- 
ment and improvement of community heart disease control programs. This 
aid has been in the nature of a seeding operation to help States in getting 
effective programs initiated and underway. The grants have made possible 
a steady although limited growth during the past few years. 

The increased funds made available by the Congress for this program 
for the current fiscal year have provided considerable stimulation in 
extending the level of control activities. Although it is too early for 
complete information as to how the States are utilizing the added monies, 
there are indications of expanding operations in a number of areas. In 
one State, for example, two new rheumatic fever clinics have been started. 
In another, a large portion of the grant is being devoted to a much 
needed study of cardiac patient home care. Still another is founding 
several diagnostic centers in a large area of the State to supplement an 



- 21 - 
existing Center and the cardiac clinics already functioning. One State 
has asked for additional payments to support a comprehensive rheumatic 
fever prevention campaign. In another instance, the increase is being 
used for participation in a coronary heart disease study now underway in 
a six-county area. 

In addition to developments such as these, there has been a 
strengthening of control programs in the States as a result of the larger 
grants. Many States are now able to train nurses, medical social workers 
and nutritionists for work in heart disease control. Also, a large number 
of professional persons skilled in heart disease methods have been added 
to State health department staffs. Another area where activity has increased 
is that of professional and lay education concerning cardiovascular diseases; 
in several States the dissemination of educational materials pertaining to 
care, prevention, and diagnosis has been developed. These activities are 
singled out for mention because they were not possible at the level of 
grants for previous years. 

Technical Services in Control 

A problem in the States generally has been a lack of sufficient 
skilled professional personnel to initiate, direct, and carry on the 
specialized segments of heart disease control programs. To help in meeting 
this problem, consultation and professional assistance are furnished to the 
States in the development and conduct of nursing, nutrition, medical 
social work, records systems, and other services necessary to heart 
disease control. 

The increased funds allotted for these technical services in 1957 
are being used mainly for an important new program: the assignment of 
full-time medical officers to States or local areas to give impetus to 



- 22 - 
their heart disease programs. Ten assignments have been made. They 
have already resulted in studies, activities, and programs within the 
States which otherwise could not have been started in the absence of 
a full-time person with medical skills. 

Our major responsibilities--leadership, research, assistance, 
and training--are all being reflected by these medical officer assign- 
ments, and at the same time the primary responsibility of the States for 
control matters is safeguarded and continuously recognized. Leadership 
is being given to heart programs in certain States which did not previously 
have a single full-time person concerned with heart problems in the 
community within the State. Promising epidemiological studies of coronary 
heart disease are now under way in three States because trained medical 
officers are available to direct the collection of data, evaluate 
screening devices, and otherwise facilitate the research. Assistance is 
provided through their services in implementing existing efforts in the 
amelioration of heart disease as a problem in the community. Finally, 
State persons are being trained in order that the public health functions 
in the community may be ultimately carried on by State and local personnel. 
The medical officers are active in whatever phases of heart disease 
control have the highest priority in their States. 

The medical officer in one State has formulated the first heart 
disease control program plan for the approval of the State Department of 
Public Health, This plan includes the establishment of diagnostic 
clinics and the initiation of studies in prevention, case finding, follow- 
up, rehabilitation, education, and epidemiological research techniques. 
The assignment of a medical officer to a municipality has meant the first 
attempt to determine if a geographical pattern of coronary disease exists 



- 23 - 
in the State; and the first plan for rheumatic fever prevention in the 
city is being evaluated. Having a full-time medical officer in another 
State has meant the development of several local heart disease control 
programs in cooperation with the county health departments. 

Other States are finding it possible, with the services of a medical 
officer assigned to them, to follow up rheumatic heart disease cases which 
had previously not been receiving needed prophylaxis; to seek effective 
screening measures for congenital heart disease among children, projects 
which had languished without adequate assistance; to cooperate more fully 
with local medical societies and heart associations; and to utilize for 
the first time rehabilitation and work measurement techniques for victims 
of cerebrovascular damage. 

It is well established that most States have data which could be 
invaluable for studies in the prevention of certain forms of heart disease, 
and for understanding the etiology of the major killer--coronary heart 
disease. These data in many States are now being used because of the 
availability of skilled persons. 

The new programs and studies being stimulated by the medical 
officers on assignment have resulted in increased utilization of other con- 
sultative services, including nursing, nutrition, and medical social work. 
Control programs are also being furthered by regioral meetings of State 
heart diseace control personnel, which are being held to present and 
discuss successful methods of operation, the development of new procedures, 
coordination of the State programs with those of local medical societies 
and the American Heart Association, and other problems of heart disease 
control. 



- 24 - 

CENTER FOR AGING RESEARCH 
The National Heart Institute has principal responsibility in the 
field of cardiovascular disease. Heart and blood vessel diseases have 
definite associations with age, however, and gerontological research has 
been an important segment of the Institute's program. 

To accelerate research activities in the field of aging, a Center fox- 
Aging Research was established at the National Institutes of Health in the 
fall of 1956, and placed administratively within the Heart Institute. A 
primary function of the Center is to assist and stimulate research investi- 
gations in aging. It also promotes coordination of intramural research on 
aging and provides liaison between the National Institutes and other organi- 
zations working in the field. Further functions are to collect and dissemin- 
ate scientific data relating to aging research and to foster the training 
of additional investigators for research on aging. The Chief of the 
Laboratory of Gerontology of the Heart Institute's intramural research 
program is serving as principal scientific advisor to the Center. 

The Center has made initial contacts with gerontological investiga- 
tors all over the country, as well as with the professional societies. Great 
enthusiasm has been shown for developing research in this field. To imple- 
ment the program, the National Advisory Heart Council has approved a pro- 
posal that selected universities, with access to the many resources needed 
to mount a well-rounded research program, be encouraged to develop large 
regional centers for research and training. Several universities have 
already expressed an interest in developing centers of this nature, and it 
is probable that one or two can be started on a small scale during the 
coming fiscal year. 

Establishment of the Center for Aging Research is a development of 
especial significance. As stated by the Secretary of Health, Education, 



- 25 - 
and Uelfare, "I am hopeful that this new effort will help bring answers 
to some of the most critical and challenging health problems of our 
times... It is important that more be done to help solve these 
problems--to help older persons to greater independence and self- 
sufficiency and a life more free of disease and disability." 

SUMMARY 
The four-fold program of the National Heart Institute is providing 
an effective approach to the problem of heart disease. During the past 
year research conducted by the Institute has continued to progress toward 
greater understanding of the cardiovascular diseases and their alleviation. 
Research supported by the Heart Institute in universities, hospitals, and 
other research institutions throughout the country has increasingly 
developed and at a faster pace, which will contribute to eventual solution 
of these diseases. Training activities being carried on, by increasing 
the supply of persons skilled in the research and clinical aspects of heart 
disease, have continued to enlarge the capacity of the nation for dealing 
more effectively with the problem. Assistance given in the development of 
community control programs has increased the heart disease activities at 
the State and local levels and has aided their sound development and 
steady growth. There is mounting evidence that the National Heart 
Institute program, joined with those of other agencies and organizations 
working in this field, is making definite headway. Expansion of the 
program in the current year has accelerated this progress and supports the 
view, held by many, that with continuously sustained efforts greater 
advances than any thus far made will be attained. 



'.•.,.,1 



- 26 - 
Of the $1,901,000 increase in obligations proposed in the budget 
for 1958, $1,469,000 is proposed for research projects in anticipation 
of a change from 157„ to 25% in the amount for indirect costs (institution 
overhead). The balance of the increase will provide $267,000 for this 
institute's proportionate share of the program services centrally per- 
formed; $136,600 for costs of retirement fund and social security contri- 
butions; and $28,400 for net costs of annualization. 



;SUIviI..IARY STATEMENT 

Director, National Institute of Dental Research 

Public Health Service 

"before 

COMMITTEE ON APPROPRIATIONS 

for 

"Dental Health Activities, Public Health Service" 



Mr. Chairman and Members of the Committee: 

A total of $6,1+30,000 is requested for the appropriation, 
Dental Health Activities, 1958, which represents a net increase of 
$^+0^,000. This additional amount is requested to cover the cc^ts 
of an anticipated increase in institutional indirect operating costs 
of research grants, for annualizaticn costs, for increased re- 
tirement and social security payments, and for increased cost of 
services furnished centrally for the National Institute of Dental 
Research. 

The emphasis of the Institute's research program vail con- 
tinue to be placed en a broad array of clinical and basic biological 
investigations. These include such studies as cause and correction 
of abnormal patterns of facial growth, the inheritance factor in 
congenital dental disease, and the prevention of dental decay and 
periodontal disease (Pyorrhea). Major attention will be given to 
the initiation of training programs to increase scientific manpower. 

In the dental research projects supported by grants, greater 
emphasis is being placed on studies of a fundamental nature. This 
trend, which was commented upon by this Committee last year, win 
continue to be emphasized by the National Advisory Dental Research 
Council as it reviews applications for research grants and makes 
recommendations regarding their activation. 



- 2 - 

The requested appropriation also provides for continuing our 
studies on the development of dental resources. These studies provide 
data on dental manpower and its distribution as well as such associated 
problems as methods of dental payments for dental services and the costs 
of dental education. 

This appropriation also provides funds for professional and 
technical assistance to develop effective methods of reducing the bur- 
den of dental disease and to furnish consultation to states and communi- 
ties in the application of these methods. 

On the basis of the $200,000 appropriated for fiscal 1957, pre- 
liminary planning for the Dental Institute building has gone forward. 
We are negotiating with the architects for design, specifications and 
drawings. 



OPENING STATEMENT 

ty 

Director, National Institute of Dental Research 
PubliC'jHealth Service 

COMMITTEE ON APPROPRIATIONS 
1959 ESTIMATE 
for 
"Den-aJ Health Activities, Put-lie Health Service" 



Mr, Ch&ir.iLan and Member cf the Cor .nit tee: 

Fiseases of the teeth and their supporting structures affect 
nearly everyone 30oner or later. Dental decay, loss of teeth, mal- 
occlusion, diseases of the mouth 1 issues, cleft lip and palate— all 

0: these bring a heavy burden cf pain, infection rnd dysfunction. 
All impair perscaal comfort and efficiency and exact a considerable 
economic toll as well,, It is to help reduce or eliminate these 
problems that the Dental Health Activities are carried on under 
this appropriation. 

The first component cf this program is research--the pursuit 
of fundamental knowledge upon which education, prevention and 
treatment can be based. This task is mighty, and the men and means 
are as yet too few. In dental research, as in other scientific 
fields, there is a crying need for more basic research and for the 
trained investigators and modern facilities that make research 
possible. 

This past year, through increased funds made available under 
this appropriation, the National Institute of Dental Research has 
helped achieve a substantial increase both in the volume and the 
scope of dental research activity throughout the country. These funds 
have permitted making a major expansion in the Research Grants Program 
within the past fiscal year. The increases also have permitted the 
initiation of a new and much needed program in our Dental Health 
Activities, namely, the Training Grants Program. 



-2- 

The expanded Research Grants Program has stimulated and encouraged 
scientists in many needy areas of investigation. Applications for re- 
search grants have steadily mounted month by month following the announce- 
ment of increased sums available for this program. The total impact of 
the increase will be more noticeable when a tabulation is made at the 
end of the fiscal year. A recent tabulation by the Division of Research 
Grants showed that, up to the date of the survey, more applications had 
been received for dental research grants than for any other time in the 
history of the program. 

An increased number of fellowships were awarded to the most 
promising students, thus increasing our future research potentiality. 

The inauguration of the Training Grants Program has permitted 
the establishment of special training centers for producing trained per- 
sonnel for the field of clinical research or academic careers. Although 
this program of training is new to dental schools, they have made re- 
markable progress in getting such training centers under way. 

DENTAL RESEARC H 
Grants for research pro.ject s; The primary purpose of the grants 
for research projects under this appropriation is to support investiga- 
tions which probably would not be undertaken if Federal funds were not 
available. In 1957, the Dental Institute is administering grants which 



-3- 

support about 24.0 projects in non-Federal institutions. These projects 
include such research investigations as the study of uptake of dietary 
factors by the tooth surfaces; the blood supply of the gingivae and 
periodontium; the structure of developing tooth structures as shown by 
X-ray microscopy; the effects of aging on the soft tissues of the normal 
mruth; the treatment and repair cf congenital deformities; and the ef- 
fects of dental health on general systemic disease. 

Each grant is reviewed by the National Advisory Dental Research 
Council. It is the duty of this group of private citizens, as you know, 
to see that the separate projects receiving support from the National 
Institute of Dental Research together make up as well-rounded a re- 
search program as funds will permit. When the opportunity of an ex- 
panded program became a reality for fiscal 1957, a special committee 
was appointed to see that special consideration was given to the stimu- 
lation of research in neglected areas. 

During the last twelve months the number of pending requests for 
research project grants has increased more than ten-fold. This situa- 
tion reflects the relatively low level of support of dental research 
activity previously and the impetus given by the increased funds made 
available for the current year. Not only the number of grants has in- 
creased but there has also been a very striking increase in the number 
of different types of institutions participating in the program. 

The increase requested in this item for 195& is to cover in- 
creased institutional indirect costs of the research projects. Approxi- 
mately the same number of grants should be supported in 19 5& as in the 
current fiscal year. 



-4- 

Research fellowships : The purposes of the Research Fellowship 
Program under this appropriation are to help promising students complete 
their graduate studies and to promote the development of mature research 
scientists. The Dental Research Institute's program is currently sup- 
porting about 60 fellowships at the predoctoral and postdoctoral levels. 
However, the number of students enrolled in advanced basic science 
courses and the number of young dental graduates who are preparing for 
research careers continues to lag behind the needs in these fields. 
Under the proposed budget this program would remain at the same level 
in 1958 as in 1957. 

In addition to the full time Research Fellowship Program, support 
is also being given to some 24.0 undergraduate dental students on a part- 
time basis. This program is an important element in the development of 
research personnel. These young students are assigned to research 
projects under the guidance of experienced faculty investigators. In 
this way they explore their interest in and capacity and potential for 
research. 

Training grants : The objective of the Training Grants Program, 
inaugurated in 1957, is to establish and support a limited number of 
training centers in dental schools throughout the country. In such 
centers there would be training in the latest methods of clinical pro- 
cedures, together with training in the basic science fields related to 
these procedures. Emphasis is being placed on indoctrinating teachers 
of clinical procedures with the disciplines of research in their field. 

The result of such training will be to produce clinical teachers 
in our dental schools who have knowledge of the field of research. This 



-5- 
will accomplish a long-needed integration of the basic biological sci- 
ences with the clinical departments of dentistry. This in turn will re- 
sult in increased activity in clinical dental research which will en- 
courage more dental students to enter research and academic careers. 
This result will ultimately improve the standards of dental treatment 
received by the people as a whole. 

Research at NIDR : The diseases and malformations of the mouth 
represent the most highly prevalent health hazards in this country today. 
Continuous fundamental research is conducted at the National Institute of 
Dental Research to obtain the knowledge needed for better preventive 
measures, better control procedures and better treatment methods. This 
operation will be carried on at approximately the same level during the 
next fiscal year. 

As the members of the Committee are well aware, the results of a 
long-range program of basic research are not readily reportable in terms 
of one twelve-month period. One development leads to another, and the 
solution of one problem raises further questions, so that it is diffi- 
cult to draw a line at any one point and say that investigation has been 
completed. Nevertheless, certain discoveries, advances in technics, and 
development of new methods indicate that progress is being made in our 
investigations which are becoming broader and increasingly more funda- 
mental in character. 

Just recently, an investigator in oral bacteriology has developed 
a selective medium for the primary isolation of oral streptococci and 
diphtheroids. This unlocks another door for us in our search for the 
relationship between dental disease and rheumatic heart disease and 
other chronic disabling conditions of man. 



-6- 

Bacteriological studies will be extended during the next fiscal 
year to answer some of the following questions: Should antibiotics be 
given to a patient with rheumatic heart disease who is to have dental 
therapy? If so, which is the best antibiotic, or combination of anti- 
biotics, to be used? Should the same plan be followed in a patient 
with rheumatic heart disease who has been receiving prophylactic peni- 
cillin for a prolonged period as in a patient who has not received such 
treatment? The Heart Institute will collaborate in this study and it is 
expected that valuable information will be forthcoming. 

Periodontal disease, that is, disease of the supporting struc- 
tures of the teeth, is receiving more attention. Studies are being 
conducted to learn more of the processes of inflammation that have a 
direct bearing on periodontal disease, which accompanies advancing 
years. For example, a new method has been devised to produce an acute 
localized inflammatory response in soft tissues of the mouth. The 
stimulus is an impulse of radio frequency electric current. Inflamed 
tissue is subjected to microchemical analysis immediately following the 
inflammatory shock and during its subsequent recovery. These studies 
can lead to understanding of the tissue chemical changes associated 
with pyorrhea. 

Some concern has been expressed about the possible physiological 
damage that could result from the use of ultrasonic dental drills, 
particularly in the case of children. In a joint investigation, the 
National Institute of Dental Research and the Naval Dental School have 
produced evidence of tissue damage in experimental animals resulting from 
the use of such instruments. The biologic effect of the newer high speed 
drilling techniques are also being studied both in humans and experimental 
animals. 



-7- 

We are also furthering our knowledge of the value of fluorida- 
tion. Earlier studies have shown the effectiveness of fluoridation 
of public water supplies as a means of preventing dental caries when 
the fluoridated water is used by children from birth. Additional evi- 
dence now shows that caries is also inhibited in children who begin 
drinking fluoridated water just prior to or shortly after the eruption 
of their permanent teeth. 

In genetics valuable information has been obtained from the 
study of a large number of inbred population groups existing in the 
Eastern half of the United States. This originated from a current 
need to secure data on which to calculate mutation rates. These studies 
have opened new vistas in the study of heredity, not only with respect 
to dental conditions, but also other medical fields. Because of the 
wide variety of supposedly inherited conditions in the present study 
group, an interest in the study has been stimulated in scientists of 
several of the Institutes, It is planned to broaden this study in 
order to determine the interrelationship of these various disease con- 
ditions, which include blood dyscrasias, mental disorders, kidney 
disease, and skeletal disturbances as well as dental disorders, 

PROFESSIONAL AMD TECHNICAL ASSISTANCE 
Professional and technical assistance is also offered to states 
and cities under the Dental Health Activities appropriation. The pur- 
poses are to develop effective methods for reducing the burden of den- 
tal disease and to furnish consultation and guidance to states and 
communities in the application of these methods. 



-8- 

This activity by the Division of Dental Public Health includes 
the collection and analysis of data on the prevalence and incidence of 
oral diseases and conditions; the development and testing of equipment, 
materials, technics and processes which appear feasible for widespread 
adoption in public health practice j and the provision of consultation 
to states and communities requesting assistance. 

Last year it was reported to this Committee that a special pro- 
cess had been developed to utilize calcium fluoride— that is, fluorspar, 
a very abandant natural chemical — in the fluoridation of public water 
supplies. The principal advantage of using fluorspar rather than one 
of the other fluoride compounds is that fluorspar is considerably less 
costly. 

We are pleased to report this year that field testing of the 
fluorspar process has demonstrated its practicability. If the new 
process were to be used in the city of Baltimore, Maryland, as an ex- 
ample, the chemical cost of that fluoridation operation would be reduced 
from $80,000 to $26,000 a year. Comparable savings could be obtained 
in other cities, depending upon the nature and size of their water 
systems . 

As you know, the reduction of dental decay that can be achieved 
through water fluoridation is as much as two- thirds. One-fourth of 
the population using public water supplies nox^ drinks fluoridated water. 
More than 1,4-00 communities with a total population greater than 30 
million are now fluoridating. Ninety-five of every 100 cities adopting 
this preventive health measure have done so on the basis of administra- 
tive decisions made by the officials of the local government. 



-9- 

About one-third of the people of this country depend upon indi- 
vidual installations for their water supply. Development of inexpen- 
sive and effective fluoridation equipment for these rural homes is 
essential if farm children are also to te protected against tooth decay. 

This year we tested the use of home fluoridation equipment in 
four homes with private wells in Montgomery County, Maryland. The hom§- 
owners are in charge of this equipment, and periodically recharge the 
stock solution container and provide finished water samples to the 
laboratory for analysis. A second project has been started in Michigan, 
using eighteen home f luoridators , These projects are planned to provide 
information on cost, interest in and acceptance of home fluoridation 
equipment and field experience in its operation. 

A series of studies have been conducted in recent years to pro- 
vide data on the continuing need for dental services among children 
who already receive regular dental care. As part of this project, 
studies are now being conducted to determine the need for dental ser- 
vice among school children in communities that either have naturally 
fluoridated water or use controlled fluoridation. 

In addition to studies of the technical aspects of fluoridation 
and defluoridation, long-range projects are being conducted to develop 
better methods of rendering dental services to older patients. Last 
year, studies were begun of the special problems of furnishing dental 
care services to chronically ill or aged patients who are institu- 
tionalized or home bound. These studies are under way at the Nevada 
State Mental Hospital, Reno, Nevada, and the Montefiore Hospital and 
Beth Abraham Nursing Home, Bronx, New York. 



-10- 
This appropriation request provides for continuation of all pro- 
fessional and technical assistance activities at the 1957 level of 
operation, plus a modest expansion and acceleration of work on the 
dental problems of chronically ill and aged persons. The increase re- 
quested would permit the development and improvement of special technics 
for the dental treatment of institutionalized or home bound patients, 
especially those who may be bedfast or unable to cooperate due to the 
nature of their illness. 

COORDINATION AND DEVELOPMENT OF DENTAL RESO URCES 
The primary goal of American dentistry has always been that of 
providing the best possible dental care for the greatest possible num- 
ber of persons who are in need of care. It is becoming increasingly 
apparent, however, that a shortage in the supply of practicing dentists 
is developing in the United States. This shortage may cause serious 
health problems unless prompt and effective action is undertaken to 
forestall it. 

There are almost 5,500 more dentists practicing today than there 
were 15 years ago, but increases in numbers of dentists have not kept up 
with our huge population growth. In 1940, there was about one practi- 
cing dentist for every 1,900 persons. By 1955, there was a much less 
favorable ratio — one to every 2,200 persons. Dental schools are train- 
ing more students than ever before, but the number of dentists entering 
practice each year is nevertheless almost 500 less than the number 
needed to maintain the current level. Should this adverse trend con- 
tinue, we will have by 1975 a dentist population of almost 95,000 but 



-11- 

a ratio of only one to 2,300 persons — the most unfavorable supply situ- 
ation since the beginning of the twentieth century. 

In cooperation with the Western Interstate Commission for Higher 
Education, the W. K. Kellogg Foundation and the American Dental Asso- 
ciation, a detailed analysis has been made of current and future dental 
supply and demand patterns in 11 Western States, Hawaii and Alaska. 
This report will be used to help plan the future expansion of dental 
education facilities throughout the western region. A similar study of 
dental manpower requirements in the 17 southern states has now been 
undertaken at the request of the Southern Regional Education Board and 
with the support of the American Dental Association and the W. K. 
Kellogg Foundation. 

An eight-part survey entitled "Dental and Dental Hygiene Stu- 
dents: Their Characteristics, Finances and Practice Plans" has been 
completed in cooperation with the Council on Education of the American 
Dental Association. It was found that no category of students was able 
to meet even half the cost of their professional education from personal 
savings or earnings. Most students looked to parents or wives for the 
money needed. Fifty-seven percent of the student body was in debt by 
the time they were graduated. This objective study of the students' 
problems in acquiring a dental education can serve as a guide for the 
appraisal of various types of financial aid available to dental students 
and dental schools. 

While more dentists must be trained, it is also important that 
their services be utilized more efficiently. The American Dental Asso- 
ciation reports that 2 out of 5 dentists are so busy that they cannot 



-12- 
treat all patients seeking appointments or must put in more hours than 
they should. Efforts are consequently being made to stimulate more 
widespread use of trained auxiliary personnel. 

The dental hygienist, for example, is trained to perform duties 
which account for as much as a fourth of the average practitioner's 
time. The dental assistant, by giving direct chair-side assistance to 
the dentist, also enables him to reduce the treatment time required for 
each patient. Under this appropriation^ therefore, pilot programs are 
being sponsored in several dental colleges to develop more effective 
methods of training dental students to work with dental assistants. 

Another important development is the application to dentistry 
of the principle of voluntary health insurance. Although prepayment 
plans covering hospitalization and medical care are now commonplace, 
prepayment plans covering dental care are in an earlier stage of de- 
velopment. Research is required to determine equitable rate struc- 
tures, effective administrative procedures, and cost and utilization 
patterns. The effect of new preventive and corrective technics on the 
overall pattern of dental care must also be considered in developing 
prepaid dental care plans. 

A study of voluntary prepaid dental care plans has therefore 
been conducted under this appropriation. Developments in the prepay- 
ment field that will help in planning of effective prepaid dental care 
plans are being surveyed and evaluated. As a part of this program, the 
Division of Dental Resources this year sponsored a national conference 
of specialists in this field. 

The fact-finding program of the Division of Dental Resources is 
proposed for continuation in 1958 at its present level. 



-13- 

Of the $4.85,000 increase in obligations proposed for 1958, $225,000 
would cover an anticipated increase from 15% to 25Jo in the allowance for 
institutional indirect operating costs (overhead) in research grants. The 
balance of the increase would meet annualization costs of current programs 
($73,900); increased retirement and social security payments ($61,300); 
and the Institute's proportionate share of additional costs of services 
centrally performed (fj.24.,800). 

In summary, Mr. Chairman, if this appropriation request is approved, 
the Dental Health Activities of the Public Health Service will go forward 
in the next fiscal year at approximately the present level. Research and 
training will remain at the same level in 1958 as in 1957, the increase 
in funds requested being necessary to cover increased overhead costs of 
the research supported. Professional and technical assistance activities 
would receive an increase in funds to permit expansion and acceleration 
of studies to develop better methods of bringing dental care services to 
chronically ill or aged patients who cannot go to the dentist's office. 
The coordination and development of dental resources activity would be 
maintained at its present level. 



SUMMARY STATEMENT 

by 

Dr. Floyd S. Daft 
Director, National Institute of Arthritis and Metabolic Diseases 

Public Health Service 

before 

COMMITTEE ON APPROPRIATIONS 

1958 ESTIMATE 

for 

Arthritis and Metabolic Disease Activities, Public Health Service 



Mr. Chairman and Members of the Committee: 

The therapeutic measures available for use against arthritis, 
diabetes and other metabolic diseases are palliative rather than 
curative. These control procedures are of tremendous importance but 
our ultimate goal — prevention and cure of these disorders— demands 
that our research efforts go far beyond an attempt to improve methods 
of palliative treatment. Because of the nature of these disorders, 
our best hope lies in fundamental research in metabolism, endocrinology 
and biochemistry and the greatest emphasis is therefore being placed 
on such studies. 

The most gratifying program development during the past year has 
been the great increase in interest in the field of diabetes. This 
stems in part from our newly established training grants program. 
Interest and activity in the basic areas which are so vital to progress 
in our understanding of the metabolic and rheumatic diseases has con- 
tinued to grow at a rapid pace. 

Noteworthy results have been obtained in all areas of our 
research program. The evaluation of the new oral drugs against diabetes 
has progressed rapidly. New and improved steroids have been developed 



- 2 - 

and tested for control of rheumatoid arthritis and related disorders. 
Moasures have been elaborated for protection against some of the fatal 
sequelae of severe burns. Particularly impressive progress has been 
made in areas of fundamental research, including the metabolism of 
sugars, the chemistry of glucagon (a hormone of the pancreas which 
has an action opposite to that of insulin), the mechanism of the action 
of insulin and the biosynthesis of connective tissue (affected by the 
rheumatic diseases), and of nucleic acids. 



OPENING STATEMENT 

by 

Director, National Institute of Arthritis and Metabolic Diseases 

Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Arthritis and Metabolic Disease Activities, Public Health Service" 



Mr, Chairman, Members of the Committee: 

BACKGROUND 

Established in 1950 under the provisions of Public Law 692, the 
National Institute of Arthritis and Metabolic Diseases superseded the 
Experimental Biology and Medicine Institute, continuing its productive 
activities in basic research along with added areas of activity in the 
specific areas of arthritis, diabetes and other metabolic diseases. 

In 1952 the new Institute received its first direct appropriation 
of approximately h million dollars, an amount which gradually has been 
increased each year as the Congress strengthened and expanded research and 
training programs. The 1957 appropriation totalled approximately 16 
million dollars. 

The stimulation and support provided by the Federal Government 
through the Institute have been felt in laboratories throughout the 
United States. Both quantitatively and Qualitatively research in the 
Institute's fields of interest has reached new high levels, from which 
cumulatively increased benefits may confidently be expected. 



- 2 - 

FACTS ABOUT THE NATURE OF THE RHEUMATIC AND METABOLIC DISEASES 

As with people, the diseases which afflict human beings have their 
remarkable similarities and distinct differences. Even though members of 
a family each may have his own personality, there are fundamental family 
traits which bind them together. The several rheumatic diseases and the 
various metabolic diseases are considered as two great "families" of 
related disorders which can be grouped together. 

Rheumati c Pi s eas e s . In this family perhaps the best-known and 
most vicious is rheumatoid arthritis, responsible for a large portion 
of the disability and crippling caused by rheumatic diseases. Other 
members of this family include osteoarthritis, gout, rheumatic fever, 
non-articular rheumatism (bursitis, neuritis, fibrositis), and the 
collagen diseases. 

Metabolic Diseases . Metabolic diseases are caused by errors or 
defects in metabolism, the basic life process by which the body converts 
air, food, and water into energy and by which growth and the replacement 
of tissue constituents are made possible. 

Diabetes, the best-known member of this large family of disorders, 
is closely associated with other less common diseases of impaired 
carbohydrate and fat metabolism. 

Gout may properly be classified in both ^he rheumatic and 
metabolic diseases since it involves a derangement of nucleic acid 
metabolism. 

Other members of the metabolic disease family are the diseases of 
the blood, including the purpuras, other disorders of the blood-clotting 
mechanism and the anemias; diseases of the liver, such as cirrhosis; 
diseases of the endocrine glands, particularly of the adrenal and 



- 3 - 

pituitary; disorders of bone metabolism, such as osteoporosis, an 
increasing problem in our aging population; and nutritional diseases, 
notably those due to vitamin deficiencies, such as beriberi and 
pellagra. Also included are a number of fatal diseases of children, 
such as mucoviscidosis (pancreatic fibrosis), phenylpyruvic oligophrenia 
and galactose diabetes (galactosemia) . Another condition in the 
metabolic disease family, obesity, shortens life and is an important 
faator in serious diseases such as diabetes and hypertensive heart 
disease. 

RESEARCH APPROACH 
The nature of diabetes, the rheumatic diseases, and the other 
metabolic diseases is such that research must include a very strong 
component of basic metabolic studies. Despite the real and gratifying 
progress which has been made in the control of such diseases as 
diabetes and rheumatoid arthritis, we still know little of their 
fundamental cause and nature. Even our control measures leave much to 
be desired. For example, even if we keep the blood sugar of diabetics 
within normal limits by diet and insulin, degenerative changes may 
continue. The basic factor in diabetes is not high blood sugar, but 
something much more fundamental and as yet incompletely understood. In 
rheumatoid arthritis we may control — by the use of cortisone, for 
example — all outward manifestations of the disease, such as inflamma- 
tion, swelling, stiffness and pain, yet the disease process itself may 
progress, with continuing and irreversible damage to the joints and 
surrounding tissues. Insulin, cortisone and other drugs are great 
boons to mankind, but the lack of information concerning basic causes 
constitutes a serious handicap to further progress. 



- A. - 

Our problem, then, is in many respects quite different from that 
found in most of the infectious diseases. In most of these the 
causative agents — bacteria, Rickettsia and viruses — have been identified, 
While great unknown areas, relating primarily to the viruses, still 
exist, the antibiotics and other agents bring about cures of a wide 
variety of infectious diseases. On the other hand, in regard to the 
metabolic and rheumatic disorders, our best available therapeutic 
agents are palliative, not curative. As a result, our major research 
effort must lie in the painstaking accumulation of basic knowledge in 
the field of metabolism. We must learn the precise chemical nature of 
enzymes. Hundreds of them exist, and more are being identified every 
year. The minute details of how all foodstuffs, v/ith the aid of the 
enzymes, are metabolized must be learned. We must isolate the hormones 
and study their mode of action. We must discover, by studies of disease 
in families and through other devices, the hereditary and other factors 
which underlie defects in metabolic processes. Only with all of these 
types of knowledge at our disposal will it be possible to achieve the 
same success against the diseases in our area of responsibility as has 
been achieved against many of the infectious diseases. 

It is most heartening to us that this Committee has consistently 
concurred in the view that the greatest emphasis should be placed on 
fundamental metabolic, endocrine and biochemical studies. 

The necessary emphasis on the research for fundamentals does not 
mean that nothing of value to those who suffer from these diseases can 
be expected in the forseeable future. In some areas, immediately usable 
findings have been produced, and the scope, variety and quality of the 
national effort in all fields of interest to this Institute make the 



- 5 - 

continuing production of immediately practical results virtually pre- 
dictable. But the ultimate answers are not in sight, and we must 
continue to stress the fundamental approach. 

'Je are most grateful for your support for expanded research and 
training activities and also for your enlightened outlook on the nature 
of our mission and on the means necessary to achieve our goal. Your 
sympathetic support has made possible the development of a farseeing 
program within which notable progress is being made. 

DIABETES 

Many investigations being carried out or supported by this 
Institute are concerned very directly with diabetes. In addition, 
great emphasis is being placed on basic studies which bear in a less 
obvious way upon this disease. Areas of fundamental research pertinent 
to the diabetes problem include the metabolism of sugars and fats, the 
nature and functions of the various hormones which affect these 
metabolic processes, the structures and precise roles of the enzymes 
involved, the complex interrelationships between the hormones and 
enzymes and the character of the controls, antagonists and balances by 
which the intricate metabolic machinery of the body is regulated. 

Oral Drugs . It was reported to this Committee a year ago that 
drugs — the sulfonamides — had been discovered which lowered blood sugar. 
The fact that these drugs were under clinical trial was noted. Since 
then every effort has been made to speed the tests of these new 
therapeutic agents. 

To accomplish this task our first inclination was to mount a 
large-scale, coordinated series of clinical trials. This would have 



- 6 - 

been in addition to the extensive clinical tests already under way, 
supported in part through funds from this Institute and in part through 
private funds. With this in mind, discussions were held with leading 
diabetes authorities in this country and with representatives of the 
firms which manufacture and distribute the oral drugs. As a result of 
these discussions, we became convinced that adequate and rapid tests 
of the toxicity of the drugs and their effectiveness against the more 
obvious signs and symptoms of diabetes were assured through the studies 
already under way. 

Instead of expanding a set of trials that were already adequate, 
we shifted the emphasis of the studies to more intensive investigations 
of the way in which these drugs operate. This is a more complex field 
of study. But, as was pointed out above, the value of these compounds 
depends not on the fact that they lower blood sugar levels, but on how 
they bring this about. 

A series of incidents from the history of diabetes research will 
serve to indicate both why attention must be focused on the way the 
drugs operate, and why we are most cautious in the claims we make for 
new drugs. 

Years ago it was found that certain drugs that could be taken by 
mouth would reduce blood sugar levels. The search for a drug that will 
relieve diabetics of dependence upon insulin administered intravenously 
is, of course, a major objective in diabetes research. This finding 
was therefore widely acclaimed as a major medical advance. 

Not until later was it found that some of the new drugs produced 
damage to the liver which prevented the liver from performing one of its 



- 7 - 

important natural functions — production of sugar (glucose) from other 
food substances. The drug had nothing to do with the diabetic process. 
It merely damaged the liver. Another set of compounds which lowered 
blood sugar levels damaged the kidneys in a way permitting sugar to 
escape from the blood into the urine with abnormal rapidity. Here, 
again, the drug harmed patients while the disease progressed untouched. 

Recollection of such incidents as this, as well as the logic of 
the current situation, has led us to increase support for more intensive 
studies of the mode of action of the new sulfonamides. 

The wisdom of the shift in emphasis in our research approach has 
been borne out by subsequent events. Clinical use of one of the oral 
drugs, carbutamide or "BZ 55", was last November virtually abandoned 
in this country because of its toxicity on long continued use. Further- 
more, the information which has been accumulating as to mode of action 
of both of the drugs under trial (carbutamide and tolbutamide or 
"Orinase") raises serious doubt that diabetics obtain any real benefit 
from their use. 

These trials demonstrate an important fundamental fact which is 
often overlooked in the first rush of enthusiasm over new drugs — 
enthusiasm which is often shared by physicians and investigators as 
well as by the lay public. This fact is that when new drugs are fully 
evaluated it is generally found — if the drugs are indeed useful at all 
and of low toxicity — that their effectiveness varies widely among 
patients. For example, age, general physical condition, and stage of 
the disease can cause wide difference in effectiveness. Such factors 
as these account for the extreme care with which useful clinical trials 



- 8 - 

must be designed and conducted, for the occasional failure of investi- 
gators to interpret results correctly, and for the cost of trials. Such 
complexities as these contribute to the fascination which medical research 
holds for scientists, to the intensity of concentration and the sustained 
continuity of effort necessary for productive work. 

In regard to the clinical effects of the agents currently under 
study, the following facts have been well established: 

1. They lower the blood sugar levels and the urinary loss of 
sugar in many elderly diabetic patients, especially if the disease is 
mild and of short duration. 

2. They are relatively ineffective in the juvenile form of the 
disease, especially in the severe diabetic, and are of no use in the 
treatment of keto-acidosis, or in the control of diabetes during 
surgical stress. 

Various theories have been proposed to account for the undoubted 
effect upon blood sugar, among these are the following: 

1. They inhibit insulinase — the enzyme which inactivates insulin. 

2. They stimulate specialized insulin producing cells to release 
such insulin as they are capable of generating. 

3. They interfere with the action or production of glucagon, a 
substance which causes the release of glucose from its storage depots. 

4. They damage the liver so as to render it a less effective 
sugar factory. 

Experimental evidence both in support of and in conflict with 
each of these ideas has been presented. There is an increasing pre- 
ponderance of data, however, which indicate that neither these 



f 9 - 

sulfonamides nor any of several natural blood-sugar lowering agents tested 
so far exert a direct insulin-like action, i.e., they do not, of themselves, 
increase sugar uptake by isolated muscle. 

Final clinical judgment as to the future role of the oral anti- 
diabetic sulfonamides will rest heavily upon the solution to the problem 
of the mode of action of the drugs. An agent that can successfully supplant 
insulin must either itself do at least what insulin does— namely, increase 
the utilization of sugar by muscle— or else it must increase the effective- 
ness or amount of insulin produced by the body. Apparently, the sulfonamides 
do not accomplish the former and there is increasing doubt that they 
accomplish the latter. 

This is not an optimistic report. It is, however, a report of 
progress. Every thoughtful competent investigation builds useful knowledge 
even though the findings demonstrate that a drug is not clinically useful. 
Concern for the sustained research in the face of set-backs impels us to 
report that successive bursts of excitement and disappointment may be 
expected before the final goal is reached. In diabetes, as in other disease 
fields, the Congress and the ordinary citizen are being brought closer 
to the world of medical research then ever before. The observers and 
supporters of research will need to share the essential faith of the 
scientist as research proceeds over its uneven course. 

Attention will now shift from studies of oral drugs for diabetes 
to some of the areas of study relating to the disease process itself. 
Some of these can be described only in terms that are somewhat technical. 
Diabetes is a most involved disease— if it can be validly described as a 
single disease — and does not lend itself to simple explanation. 



- 10 - 

Some generalizations, however, should lend coherence to these diverse 
lines of study. Diabetes is usually first recognized by a breakdown 
in the utilization of sugar in the body. Consequent upon this failure, 
a wide variety of other effects ensue, including incomplete breakdown 
of fats. The most detailed knowledge of precisely how the sugars and 
fats are used is relevant to diabetes. The most important natural 
substance related to diabetes is insulin. The biochemistry of insulin, 
therefore, has obvious importance. Because of the complexity of the 
problem, however, the metabolism of other classes of substances and the 
biochemistry and interrelations of other regulators, especially hormones 
of the pituitary and adrenal glands, are an important part of the whole 
picture. 

Metabolism of Sugars . The body of knowledge relating to the 
metabolism of carbohydrates, already vast, has continued to increase 
through the efforts both of NIAMD grantees and of intramural investi- 
gators. Increasing efforts have centered about the biological 
relationships of the 5-carbon sugars, the pentoses, to the more familiar 
hexoses which contain 6 carbon atoms. The enzymes which catalyze many 
of the reactions of these compounds have been purified and the reactions 
have been isolated and studied. The sugar, xylulose, formerly believed 
to occur uniquely in the urine of patients with the rare familial taint, 
pentosuria, has been shown to be a constant though minor constituent of 
normal urine. Pentosuria has at times been confused with diabetes, but 
unlike diatetes it is a harmless condition. 

The very provocative discovery has been published and extended 
that an important sugar in mammalian biochemistry, ribulose diphosphate, 
is also a key factor in photosynthesis, the fundamental life process of 



- 11 - 

plants. 

Glycogen, the storage form of sugar in animals, has been the subject 
of intensive study by newer methods, and advances have been made in our 
knowledge of the manner in which it functions as the body's storage 
form of sugar. 

Insulin Structure . Of the several endocrine products concerned 
with diabetes, insulin is the most prominent. The structure of this 
hormone, as derived from pig, sheep and beef, had previously been es- 
tablished and has now been studied in other species, including the whale. 
Interestingly, although differing in different species, all the 
dissimilarities that have been recorded occur in one small series of 
three amino acids in the vast complex of fifty-one amino acids of which 
insulin is comprised. 

By analogy with the pituitary hormones, which in common with 
insulin are protein in nature, there existed some hope that a portion of 
the molecule might be the essential part and carry the physiological 
activity of the whole. The unlikely possibility has been considered, 
further, that this hypothetical small essential portion of the molecule 
might be effective when given by mouth. These possibilities seemed 
somewhat remote at the beginning and have become less and less likely 
as further studies have been made. Very small chemical changes in the 
large insulin molecule have in most cases destroyed its physiological 
potency. 

Nevertheless, synthesis of portions of the large insulin molecule 
have been undertaken because such compounds, even though not useful as 
oral forms of insulin, might be extremely valuable tools in relating 



- 12 - 

structure to physiological activity and in learning more about the mode 
of action of insulin. Our first attempts to synthesize certain specific 
portions of the molecule must be reported as failures but work on this 
problem is being vigorously pursued. 

Structure of Glucagon . Uithin the past year the entire structure 
of glucagon has been elucidated. Glucagon, a protein hormone, arises 
in the pancreas, as does insulin, but its chemical structure is very 
different and it has been shown to be biologically distinct. Although 
glucagon has an effect opposite to that of insulin in that it causes a 
rise in blood sugar concentration, its mode of action is fairly well 
defined and it is known not to exert a direct antagonism to insulin 
action. 

Other Hormone s. The hormones of the anterior pituitary gland, 
which act antagonistically to insulin, have also attracted much study. 
Growth hormone, when derived from beef pituitaries, had previously been 
shown to cause diabetes in dogs but to be without effect on humans. This 
represented a very unusual situation since hormones derived from one 
species are in general active in all. Monkey and human growth hormones 
have now been isolated by an NIAMD grantee at the University of 
California who has shown that the product derived from the monkey is 
active in man. The therapeutic implications of these discoveries are 
being explored. 

Enzymes in Diabetes . The effects of insulin or lack of it upon 
the enzyme architecture of the organs of the body is a fairly new area 
of study. Thus the enzyme (glucose-6-phosphatase) responsible for the 
last step in the generation of glucose by the liver has been shown by 



- 13 - 

a grantee at Harvard University to be markedly increased in activity as 
a consequence of diabetes. Similarly, certain of the enzymes concerned 
with the transformation of the amino acid, tryptophan, into the vitamin, 
niacin, a normal process in most species, are strikingly altered in the 
diabetic state. 

Insulinase . That insulin is destroyed in the animal body has 
long been known. The nature of the apparently fairly specific enzyme 
activity, termed insulinase, responsible for this destruction, has been 
studied. A number of agents which inhibit insulinase activity in test 
systems have now been discovered and are being investigated in intact 
animals by grantees at several institutions. Research in this area is 
being fostered since the possibility exists that if insulin destruction 
could be retarded diabetics might be regulated with less insulin. 

Diagnosis and Early Treatment . Early diagnosis of diabetes has 
long been a major goal since the disease, when uncontrolled by diet, 
insulin, or by a combination of the two, is much more serious in its 
effects. Investigators in the Chronic Disease Program of the Bureau of 
State Services have been pioneers in this field. An NIAMD grantee at 
the University of Michigan has recently suggested a method of determina- 
tion of diabetes "susceptibility". In families, some members of which 
are normal, some frankly diabetic and others "prediabetic" (not frankly 
diabetic but with poor glucose tolerance), a fourth group showed 
entirely normal responses to glucose tests except when given cortisone. 
It will require a number of years to determine the validity and clinical 
usefulness of this suggestion that a diabetic tendency might be 
"unmasked" by testing with cortisone. 



- H - 

In connection with the determination of "susceptibility" to 
diabetes or the diagnosis of the disease in its early stages, the hope 
exists of devising a means of its prevention or the arrest of its 
progress. Although studies are in progress of the effects of giving 
very small doses of insulin to patients in the earliest diagnosable 
stages of diabetes, the hope of arresting the progress of the disease by 
this means seems rather slim. Several years of observation will be 
required, however, before the measure of success or failure can be de- 
termined with certainty. 

Mechanism of Action of Insulin . Evidence has been accumulating 
over the past several years which suggests strongly that one, and perhaps 
the primary, action of insulin in carbohydrate metabolism is to expedite 
the passage of glucose across cell membranes — from the blood to the 
muscle and other tissues where it is utilized for the production of 
energy. With5.n the past year, grantees in several institutions have 
presented additional evidence strongly supporting this concept. On the 
one hand, this represents a most gratifying increase in knowledge j on 
the other, if our conclusions are correct, it indicates limits to the 
techniques available for further progress in this field, since intact 
membranes will be necessary and consequently cell-free extracts cannot be 
expected to be useful. 

ARTHRITIS 

Here, again, as in diabetes research, major emphasis has been 
placed on basic metabolic endocrinological and biochemical investigations. 
The chemistry of connective tissue is being studied since this is the 
substance attacked by the rheumatic diseases. The formation and 



- 15 - 

metabolism of connective tissue components and the enzymes involved are 
being investigated. Information is being gathered on the site and mode 
of action of the adrenal steroids and other hormones. The fundamental 
defects and precipitating factors underlying the disease processes are 
being sought. In addition, therapeutic measures are being evaluated. 

New Steroids . Stimulated first, in 1949, by the discovery of the 
beneficial effects of cortisone in the treatment of rheumatoid arthritis, 
and given additional impetus two years ago by the development of prednisone 
and prednisolone, active searches are underway for better and less toxic 
drugs. Several new steroid compounds have been announced within recent 
months which are the products of intensive research into the possibilities 
that the beneficial effects and the unwanted dangerous side effects 
inherent in the parent steroid molecule could be separated. 

One of these new synthetic compounds, triamcinolone (called "Orion" 
by its manufacturer) is nov; being tested by our clinicians in the Clinical 
Center at Bethesda as well as by a number of grantees — at Columbia 
University, the Hospital for Special Surgery in New York, and the University 
of Pennsylvania in Philadelphia. This drug, on the basis of preliminary 
clinical studies, appears to be as potent in suppressing the symptoms of 
arthritis as is prednisone. Claims have been advanced for greater freedom 
from side effects but much longer use in many more patients is necessary 
before reaching definite conclusions on this point. 

Still another new synthetic steroid has recently been announced. On 
the basis of laboratory tests it also is claimed to be an improvement over 
currently employed steroids. This drug, a methyl derivative of prednisone, 
named "Medrol" by its makers, is currently undergoing clinical tests, 
results of which have not as yet been disclosed. 



- 16 - 

Failure to Halt Disease Process . As has been pointed out, the 
treatment of patients with metabolic and rheumatic diseases with the 
presently available drugs is palliative rather than curative. This 
observation appears to apply with particular pertinence to treatment of 
arthritics with steroids and other drugs. It has become increasingly 
apparent even within the past year that the disease process in rheumatoid 
arthritis may continue to advance even while the outward signs are sup- 
pressed by drug therapy. 

This does not mean that the drugs are valueless, basing of pain is 
in itself a tremendous benefit to the sufferer from the disease and with 
the suppression of inflammation, swelling and pain, comes the ability to 
prevent a large portion of the otherwise almost inevitable deformities 
and permanent crippling. Even in cases where crippling has occurred 
before adequate therapy was instituted, the use of the steroids and other 
drugs has made it possible to carry out rehabilitation procedures. These 
have resulted in returning many crippled individuals to gainful occupations 
and to nearly normal and very useful lives. 

Our failure to halt the disease process in a large number of 
individuals does indicate, however, the complexity of the problem which 
we face. Even more important, it brings very sharply to our attention 
the necessity for other more basic approaches to the solution of the 
rheumatic disease problem. 

Connective Tissue Research . Many of the rheumatic diseases have in 
common the fact that they affect the connective tissue, the material which, 
in tendons, ligaments, cartilage, skin and the lining of ths joints, forms 
the supporting structure of the body. Under the microscope, connective 
tissue is seen to be composed of fibers imbedded in a non-fibrous mass. 



- 17 - 

This non-fibrous material is called ground substance. An important 
attaok on the rheumatic diseases is now centered on obtaining more basic 
scientific information about connective tissue, identifying precisely its 
fundamental components and determining their functions, from the study 
of both normal and diseased tissues. 

In work on the definition of connective tissue components, at- 
tention has been focused on the ground substance fractions, hyaluronic 
acid, chondroitin sulfate and the hexosamines, since they appear to play 
more dynamic roles than other materials in the metabolism and development 
of connective tissue. As an example of this work, a grantee at Columbia 
University has found that the chondroitin sulfate in skin does not 
contain glucuronic acid as do other connective tissues but iduronic acid, 
a sugar never before found in animal protoplasm. Analysis of its 
characteristics should lead to some understanding of its special role in 
its unique location. 

An extremely important development in the investigation of function 
of connective tissue components has been the recent successful demonstra- 
tion by NIAMD scientists and grantees of the biosynthesis by connective 
tissue of hyaluronic acid, one of the ground substance fractions. This 
was accomplished first in tissue cultures of synovial tissue taken from 
human joints during operations and very recently in cell free extracts 
of umbilical cord and placenta. Following this achievement, the investi- 
gators were able to determine that some patients with rheumatoid 
arthritis have in their serum a factor, as yet unidentified, which 
interferes with the synthesis of hyaluronic acid by joint tissue. 

This constitutes a small but important start on the task of 



Tsui- 



- 18 - 

determining the chemical structure of all connective tissue components, 
delineation of the steps by which they are normally synthesized in the 
body and the identification of the biochemical and metabolic defects in 
patients with the rheumatic diseases. 

OTHER METABOLIC DISEASES 

Fatal Infections Following Burn s. The parts played by clinical 
observations and by animal and other laboratory studies, and the necessity 
for both approaches, is nowhere better illustrated than in our investiga- 
tions of measures of therapy for patients with severe burns. 

Also illustrated by these investigations is the multiplicity of 
uses of certain of the new therapeutic agents, in this case, cortisone. 
This adrenal steroid, as you know, gives benefit to sufferers from 
rheumatoid arthritis and some other diseases. Drawbacks to its use are 
that it increases susceptibility to infection and that it sometimes 
causes transitory diabetes. These very defects have made this drug 
useful in researches in other fields, such as improvising a test for 
diabetes susceptibility, mentioned earlier, improving tests for the 
presence of live poliomyelitis virus in vaccines and, as will appear, 
in simulating certain human disease conditions in small animals. 

That fatal shock in patients may follow burns or other injuries 
has long been known. The administration of blood or plasma does much to 
prevent or overcome this condition. MIAMD investigators several years 
ago, in searching for a simpler treatment, carried out tests in mice and 
found that oral salt and soda would prevent death from shock in these 
animals. The study was then returned to the clinic and last year it was 
my pleasure to report to you that in human patients, as well, the 



•:. 1 



■;.-! 



- 19 - 

administration of salt and soda by mouth had greatly reduced the number 
of deaths from shock following severe burns. The importance of this 
method of treatment in the event of a large-scale catastrophe is obvious. 
If the number of casualties were large, intravenous therapy would be 
impractical and adequate supplies of blood or plasma probably would not 
be available. 

During the past year, further significant findings have been made 
in this study, this time relative to deaths of severely burned children 
occurring after the shock period has been successfully passed. The NIAMD 
physician in charge of the clinical work determined, from blood cultures, 
that in virtually every patient who died after the acute shock period 
there appeared an organism called Pseudomonas. The problem was brought 
back to the laboratory, where efforts were made to infect laboratory 
animals with the organism. These attempts failed in all except burned 
animals until the stress of burning was simulated by the administration of 
cortisone. Animals so treated could be infected by Pseudomonas. Work 
then proceeded to find a suitable treatment for prevention of this in- 
fection. Common antibiotics were not useful. One uncommon antibiotic, 
polymixin B, did do the job, but is too toxic for common use. The most 
effective agent in the treatment of the burned or Pseudomonas infected 
animal has proved to be human gamma globulin. Proved effective in the 
laboratory, this therapeutic agent is now scheduled for clinical testing, 
and may prove effective in saving additional numbers of human lives now 
lost due to the effects of post-burn infections. 

Detection of Intestinal Bleedin g. A method of immensely practical 
value for the clinical detection and measurement of blood loss from the 



- 20 - 

gastrointestinal tract has been devised by NIAMD scientists. A significant 
advance in diagnostic techniques, the new method is much more effective 
and precise than older procedures, including x-ray, for localizing the 
site of bleeding in the intestines. The new system involves tagging the 
patient's red blood cells with radioactive sodium chromate, and the 
analysis of stools and samples obtained by passing a tube down the in- 
testinal tract. In their work the NIAMD investigators have shown that it 
was possible for a patient to lose as much as a pint of blood a day without 
detection by commonly used tests, but the new method easily reveals the 
loss of a fraction of this amount, as well as the precise location of the 
site of bleeding. The method's unusual value already has been demonstrated 
in six patients in whom sources of bleeding previously had been missed by 
standard methods. In each of these cases the blood loss was detected 
and the site of bleeding determined, making possible surgical correction 
of the diseased conditions. 

Enzymatic Synthesis of Nucleic Acids . An outstanding achievement 
of the year which relates not only to diabetes but also to innumerable 
other problems is the accomplishment by one of our investigators at 
Bethesda and by a grantee at New York University, of the synthesis of 
nucleic acids by enzymes isolated from living cells. The nucleic acids 
serve, among other functions, as the reservoirs of chemical information 
essential to the cell and to its progeny. They are believed to be the 
materials which are responsible for genetic transmission of heritable 
characteristics and defects, among which is diabetes. They also are 
responsible for the ability of a cell to generate, without variation, 
identical molecule after molecule of a protein such as insulin. Knowledge 



- 21 - 

of their mode of synthesis is, therefore, regarded as a noteworthy ac- 
complishment. 

PROGRAM DEVELOPMENTS AND PLANS 

The budget for this Institute was increased in fiscal year 1957 
from $10,840,000 to $15,885,000. Of the $5,04.5,000 increase slightly 
more than $1,000,000 has been used to strengthen and expand research in 
the broad field of diabetes, including the evaluation of the new oral 
drugs and the acceleration of fundamental metabolic, endocrine and 
biochemical investigations related to diabetes. An additional amount — 
in excess of $600,000 — has been utilized to accelerate basic studies 
on the nature and functions of hormone systems and investigations of 
other fundamental processes which lie at the root, not only of diabetes, 
but of all metabolic diseases. 

The upsurge of interest in the field of diabetes has been particu- 
larly noteworthy and gratifying. Grants for research projects clearly 
identifiable as being in the field of diabetes have approximately doubled 
in the past year. At the present time individuals who are interested 
and competent in this field are being fully supported. 

Interest in the fields of metabolism, endocrinology and biochemistry, 
as related not only to diabetes but also to other areas of responsibility 
of this Institute, has been increasing very rapidly for the past several 
years. Because of the basic position of these fields of scientific 
endeavor relative to progress in all areas of medical research, an 
intensification rather than a slackening of interest and activity in 
these areas is to be expected in the years ahead. 

An increase of $900,000— from $950,000 to $1,850,000— has been 
available in fiscal year 1957 for training grants and has been utilized 



- . 22— 

with results of great benefit to our entire program. It appears certain, also, 
that the benefits have not as yet been fully felt. The total funds available 
in this program have permitted us to strengthen diabetes programs in £1 medical 
schools, a significant proportion of the total number of four-year schools in 
this country. It has also permitted the strengthening, to a lesser extent, 
of teaching programs in arthritis and in metabolic diseases other than diabetes. 

With respect to the effectiveness of the new arthritis training grants 
program, the president of the American Rheumatism Association recently report- 
ed that in 195>U, when it x^as first initiated on a small scale, only 8 medical 
schools, less than 10 percent of the total number, had sub- departments devoted 
to the teaching and conduct of research in the rheumatic diseases. At the 
present time, due largely to the training grants, ^6 medical schools have 
active training programs in this field. 

As training programs in diabetes, in arthritis and in other metabolic 
diseases get under way a great increase in research interest in the same 
subjects invariably occurs. 

Of the $1,930,000 increase in obligations proposed in our budget for 
fiscal year 1958, $689*000 represents an expansion of our research grants 
program. This increase will permit the payment of approved project requests 
which could not otherwise be activated and will provide a measure of support 
to additional projects specifically programmed in arthritis and diabetes. 
The balance of the increase is proposed in anticipation of a change from 1$% 
to 2$% in the amount allowed for indirect costs ("overhead") of the total 
research grants activity (0708,000) \ to meet this Institute's proportionate 



- 23 - 

share of supporting additional costs for research services centrally performed 
(^iiljOOO) j for payment of retirement fund and Social Security costs Ql29>000)j 
and for annualization costs of our current operations (063,000), 

CONCLUSIONS 

A productive program in diabetes, arthritis and other metabolic diseases 
is well under way. Studies directly related to specific clinical disease 
entities are being furthered, but the greatest emphasis is being placed on 
fundamental studies in metabolism, endocrinology and biochemistry. Only with 
the knowledge derived from such researches will it be possible to pass from 
our present stage, where control measures against diabetes, arthritis and 
metabolic diseases are our greatest accomplishments, to the stage where pre- 
vention and cure of these diseases may be achieved. 

Research accomplishments during the past year have been most gratify- 
ing. They lie in part in improved control measures and in an improvement of 
our understanding of specific diseases, but more particularly they represent 
substantial increases in our knowledge of the basic metabolic processes 
occurring in the body. 

With the increased interest and activity in the areas of research for 
which this Institute is responsible, steming in part from our newly establish- 
ed training programs, we have come to a period of challenging opportunity. 
The base has been established from which great strides forward may be predict- 
ed with confidence. 



SUMMARY STATEMENT 

by 

Director, National Institute of Allergy 
and Infectious Diseases 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Allergy and Infectious Diseases Activities, Public Health Service" 

Mr. Chairman and Members of the Committee: 

The National Institute of Allergy and Infectious Diseases 
(formerly the National Microbiological Institute) supports and con- 
ducts research on the infectious and parasitic diseases and on allergy, 
through direct operations, grants, and fellowships. These diseases 
are the chief causes of illness in the United States, and some of 
them lead to disability of long duration. 

Research on viruses continues to be productive and promising. 
Many new viruses are being discovered, and we are learning through 
virus research more about the fundamental processes of all living 
matter. By using tissue culture it is possible to follow the course 
of viruses through selected human populations, to identify them with 
specific illnesses, and to learn how they spread. A new experimental 
vaccine against one form of acute respiratory illness ("grippe") has 
proved gratifyingly effective. The exploration of the destructive 
effect of certain viruses on cancer continues. 

Encouraging progress is being made in breaking up microorganisms 
in order to provide better and less toxic vaccines. An experimental 
trial of a tuberculosis vaccine produced in bhis manner is under way. 



- £ - 

The program on allergy, a new responsibility of this Institute, 
has begun vigorously. Growing interest in the use of germ-free animals 
has been signified by increased requests for grant assistance and by 
intensification of direct research. 

There is an acute need for additional highly qualified scientists 
to carry forward the research programs which are now so promising. It 
is imperative that more of our brilliant young people be stimulated to 
enter the field, and that opportunities be provided for their academic 
development . 

Funds requested for fiscal 19^8 total $17,1+00,000. This is 
an increase of $1+,101,000. It is proposed to use -J2. , 612 , 000 for 
grants-in-aid of research, and i>650,000 for the initiation of a train- 
ing program. The remainder will be used in extending our direct 
research, particularly in allergy and virology. 



OPENING STATEMENT 

by 
Director, National Institute of Allergy 
and Infectious Diseases 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
for 
"Allergy and Infectious Diseases Activities, Public Health Service 1 



Mr. Chairman and Members of the Committee: 

Introdu ctio n 

The National Institute of Allergy and Infectious Diseases, formerly 
the National Microbiological Institute, supports and conducts research on 
the diseases caused by microorganisms (viruses, bacteria, fungi, protozoa, 
and parasitic worms), and on fundamental aspects of the reactions of the 
infected host to the microorganism or its products. It has a primary 
responsibility for the conduct, stimulation, and support of research on 
allergic diseases. The ultimate goal is improvement in diagnosis, pre- 
vention, and treatment of human illnesses directly or indirectly caused 
by parasitic organisms and allergy- producing substances. 

The infectious diseases are the greatest cause of illness and 
absenteeism from schools and industry. In infancy and early childhood 
they are the most frequent cause of death; in older children and pre- 
adults they rank among the first four causes . The allergies affect many 
millions of people of all ages, over a million of them to a severe degree. 
Beyond the immediate effects of infectious and allergic diseases there is 
a poorly understood cumulative or delayed action which is increasingly 
regarded as contributing to the development of certain chronic illnesses 
that occur later in life. 



- 2 « 

Despite our achievements in the prevention and treatment of infec- 
tious diseases, there are still large numbers of persons who, at any given 
time, suffer from one of the illnesses of this group. The appropriation 
increase requested is to provide support for the development of promising 
leads which have resulted from research in the recent past, to extend our 
efforts into these two major areas, and to assist in the production of 
additional highly qualified research workers. 

This statement indicates some of the accomplishments as well as 
some of the important problems requiring attention in the broad areas of 
the allergic and infectious diseases. 

Viruses and Virus Vaccines 
Virus discoveries.- Some of the greatest advances in medical 
research are being made in the study of viruses, the smallest known forms 
which have the attributes of life. Scientists all over the country are 
pushing forward the frontiers of our knowledge of the process of life 
itself, using these minute microorganisms as tools. At the same time, 
we are learning more about how to deal with them as disease-producing agents. 
Discoveries of an increasingly significant nature are coming rapidly as new 
and revolutionary methods are evolving for dealing with viruses, First of 
these techniques was the use of the chick embryo, which enabled us to 
learn how viruses invade cells and what they do after they get in. This 
technique made possible the vaccines against encephalitis, mumps, and 
influenza. Next was the suckling mouse, which gave us the entry to the 
study of the Coxsackie viruses, to be mentioned later. Now we have tissue 
culture - receiving its original impetus as a technique for cancer study, 



- 3 - 

it has created a wide forward surge in virus research. Tissue culture 
has given us the newly recognized adenoviruses (about which more will be 
said in this statement) , and other viruses whose significance remains to 
be discovered, a whole class of these now being designated as PXHO 
(enteric, cytonathogenic, human, orphan) viruses. 

Those newly discovered viruses which have been definitely identi- 
fied with specific diseases produce at least the following illnesses, 
and doubtless many others which will come to light: 

Exudative pharyngitis 
Non-bacterial conjunctivitis 
Epidemic keratoconjunctivitis 
Herpangina 
Pleurodynia 

Grippe and severe cold-like illness 
Aseptic meningitis and polio-like 
conditions 

There are wide variations in degree of illness, from severe febrile 
conditions such as pneumonia, to complete absence of detectable disease 
with only antibody production to indicate that infection occurred. 

A denovirus vaccines .- During the past fiscal year, two success- 
ful investigations on a new vaccine for certain respiratory virus infec- 
tions have been completed, Both concerned the adenoviruses, formerly 
called APC viruses. The adenoviruses cause a variety of illnesses, 
which resemble or are associated with severe colds, grippe, influenza, 
and streptococcal sore throat. These infections are widely prevalent 
and easily transmitted. There are many types of viruses in the group, 
and the vaccines dealt with a single type in one instance and with three 
types in the other. 



- h - 

The first study of the protective value of adenovirus vaccine, 
which was in cooperation with an investigator from the Johns Hopkins 
University, was carried out with the aid of 83 volunteers at two prisons. 
Vaccine against type 3 adenovirus was given to IS of these, and the other 
38 were untreated. Later, each volunteer was exposed to live virus. In 
the vaccinated group only 10 per cent became ill as contrasted with 71 
per cent of those unvaccinated. 

The second study was in collaboration with the U. S, Navy, and 
took place at the Great Lakes Training Center. Vaccine against adeno- 
virus types 3, h, and 7 was administered to lj.,000 recruits. By compar- 
ing antibodies and incidence of illness among those vaccinated with 
12,000 unvaccinated, it was found that a substantial reduction in acute 
febrile respiratory illness had been achieved. 

These vaccines will not prevent the condition generally regarded 
as the "common cold" but they are a promising step toward practical 
reduction in illnesses of the "grippe" type. 

These vaccine studies required the close cooperation of laboratory 
scientists and epidemiologists, and such teams are pushing ahead with the 
investigation of the recently discovered adenoviruses and with others 
newly coming to our attention. 

Salivary gland virus .- One of these new agents is the "salivary 
gland" virus. This, like the adenoviruses, has come to light during studies 
on tissue cultures which have yielded previously hidden or latent viruses. 
This particular one is often associated with the adenoviruses found in 
adenoids. Sometimes a culture of adenoid tissue will yield both adenovirus 



- 5 - 

and the salivary gland virus. The latter is widespread^ perhaps k out of 5 
people are infected with it at some time in life. It may persist in cells 
for long periods. This persistence and wide prevalence, and the fact that 
it occurs in other areas in the body, suggest that it may relate to chronic 
and other illnesses whose origin is still obscure. Further studies are 
going on to show to what degree the salivary gland virus is similarly 
identifiable with specific human illnesses. 

Scientists are eager to explore the possibilities that other 
viruses, too -- some as yet unknown — may be causally identifiable with 
chronic or debilitating diseases. 

Coxsackie viruses .- Another group of viruses which have been 
known for only a few years, and about which new knowledge is constantly 
being uncovered, are those called the Coxsackie viruses. It has been known 
for 3 or h years that they cause two specific epidemic diseases, pleuro- 
dynia and herpangina. More recently, they have been implicated in illnesses 
resembling poliomyelitis but without residual paralysis. Still more recently 
there have been two interesting and quite important discoveries involving 
these viruses ; these are discussed below* 

Virus and cancer .- One of these has been the demonstration of 
the ability of certain strains of Coxsackie viruses to destroy cancer 
tissue under experimental conditions. The cancer cells now widelv used 
for tissue culture -- called HeLa cells — have been grov/n in the abdominal 
cavities of rats, and later Coxsackie viruses have been introduced into 
these rats. The viruses developed an ability to destroy the cancer cells 
rapidly and completely. They were equally active when given by vein or 



- 6 - 

injected directly into the abdominal cavity. A study is now in progress, 
in cooperation with the National Cancer Institute, to determine the effects 
of these viruses in selected cases of human cancer. These investigations, 
using the Coxsackie viruses, resemble the earlier ones previously reported 
to the Committee, in which the adenoviruses were employed. The human trials 
with the viruses of the Coxsackie group are in the beginning stage. 

There is growing interest in the possibility that viruses may be 
involved in the cause of certain cancers. In lower animals, this is 
known to be so. Work now under way will give us more information regard- 
ing this important question as it concerns human cancer. 

Crystalline viru s.- The other development has been the preparation 
of the virus in crystalline form, iiany years ago Dr. Wendell Stanley 
obtained pure crystals of the virus which causes mosaic disease in tobacco 
plants. Recentr^ his co-workers crystallized the virus of poliomyelitis 
from tissue cultures. The recent work in the National Institute of 
Allergy and Infectious Diseases with Coxsackie virus is the first time 
that a virus has been obtained in crystalline form directly from an 
infected animal. This is the sort of precise scientific study which may 
eventually help to disclose the chemical nature of viruses and contribute 
to our understanding of the fundamental nature of infection. 

Partial virus synthesis .- There have be^n other accomplishments 
which bring us closer to comprehending what a virus really is. One of 
these, by a grantee of the Institute, has been the coupling of fragments 
from two different strains of the tobacco mosaic virus to form a new 
virus strain. This means that a complete virus with characteristic 



- 7 - 

attributes has been created artificially by combining two inert building 
units. Another related achievement has been the demonstration that the 
nucleic acids of viruses •-- the ultimate constituents which determine 
the nature of the virus and what it will do — are chemically the same 
in different strains of a given virus, even though these strains behave 
differently. Evidently these differences in behavior must be related 
to structural features of the nucleic acid which are as yet undetermined. 
Nucleic acids of different viruses -- as distinguished from separate 
strains of the same virus -- are chemically distinct. 

More is being learned about what a cell requires in order to 
produce virus material. Unlike higher forms of life, viruses do not 
multiply by simple division and growth. Instead, they disarrange the 
infected cell's activities in some way which causes the latter to produce 
virus particles instead of normal cellular materials. It has been shown 
b' r scientists of the Institute that there are three critical factors in 
the production of poliovirus by certain cells in tissue culture. These 
are: a sugar (glucose), an amino acid (glut amine), and salts. The cell 
will survive without these factors, but will produce virus only when they 
are supplied. 

More progress in virus research and related areas will continue to 
be forthcoming. The funds made available by the Congress last year, and 
those requested for fiscal year 195b 1 are an important factor in assuring 
the proper exploitation of the present momentum. 



Antigen Fractionatio n 

While some scientists are taking viruses apart and putting them 
together again, others are breaking bacteria down into their basic elements 
in order to separate out those portions which are useful to us as vaccines, 
and to discard the rest. An NIAID team has been in the forefront of this 
work for several years j they are now using S almon ilia enter id it is , a common 
cause of food poisoning, as a model for their experiments. The main mass 
of bacterial substance is removed from its normal location inside the walls 
of the bacterial cells, and the empty capsule thus created is purified by 
chemical means. Toxic and irritating elements are thus removed, and the 
remaining cell wall is used to make a protective vaccine for experimental 
animals. The procedure is called antigen fractionation. Purification of 
vaccines is an important goal in infectious disease research, and this is 
a significant advance. 

Tuberculosis 

An important disease for which better prevention and treatment are 
needed is tuberculosis. Though it has been decreasing steadily, there were 
more than 100,000 cases reported in 195k, and over 16,000 deaths. Preven- 
tion thus far, under conditions in the United States, has required laborious 
case-finding, isolation, and the use of treatment to reduce infectiousness. 
What is needed is a safe method of immunization which can bo widely adminis- 
tered, and more effective agents for the cure of active cases. 

Unfortunately, the body does not react to infection with the tubercle 
bacillus in the manner that characterizes its response to many other micro- 
organisms. The clear-cut and lasting immunity which allows us to control 



- 9 - 

smallpox, diphtheria, typhus, and other epidemic afflictions does not 
occur in tuberculosis. Once a person is infected, he is likely to remain 
so for a very long time; the bacteria may be completely dormant for years, 
or nay show renewed activity without warning. 

Infected individuals may be identified by their positive reaction to 
the tuberculin test. Studies in the United States have shown that the 
tuberculin-positive members of our population ultimately account for the 
great majority of active cases of the disease. For example, in the Navy, 
an investigation of more than 75,000 men indicated that in three years the 
rate of tuberculosis among tuberculin positives was more than six times 
that among negatives , 

The significant practical point is this: the tuberculin positives, 
who account for the great majority of our tuberculosis illness, cannot be 
immunized by any method available today. This is because any such procedure 
exposes the tuberculin positive person to an unacceptable hazard -- the 
likelihood of acute flare-up. Thus, immunization as we know it now — 
BCG for example -- can be used only in individuals who are first shown 
to be tuberculin negative -- and in the United States today these are not 
the people who are going to get much tuberculosis or who constitute danger 
to others by spreading it. 

The answers which we are seeking must therefore depend upon 
(a) improving our understanding of what makes the human react as ho does 
to the tubercle bacillus, -.nd (b) devising a letter vaccine than any now 
available. The first approach lies in the field of basic p.llergy and 
immunology, one which is now being vigorously developed by our Institute; 
the second is being advanced by studies now under way, by MIAID scientific 



- 10 - 

staff and grantees, to extract from the tubercle bacillus those components 
which immunize, eliminating those which produce harmful reactions. 

Among the nearly 50 research projects supported by the Institute in 
the area of tuberculosis at a total cost of more than three-quarters of a 
million dollars, both immunization and therapy are receiving attention. 
The antigen fractionation technique, mentioned previously, is being 
applied to the problem of tuberculosis immunization in the laboratory, 
the pilot plant, and the clinic. And new drugs, plus more effective use 
of drugs already known, are uncter close study in experimental animals and 
in man. 

As knowledge increases regarding all phases of tuberculosis research, 
ranging from the fundamental problems of host reaction to infection, all 
the wa T r to the practical ones of vaccine and chemotherapy trials, answers 
to the continued threat of this disease will emerge more rapidly. Until 
more adequate knowledge is available, it is important to emphasize that 
there is not now in hand a specific preventive that can be safely and 
effectively used in the population of the United States, nor a universally 
applicable, solidly reliable cure. 

Hypogammaglobulinemia 

If an}/ vaccine is to be effective, it is essential that the person 
vaccinated be capable of responding in the manner expected. Recently our 
clinical scientists have completed a study of a patient who was consti- 
tutionally incapable of the normal response, either to vaccines or to 
living microorganisms. This condition is called hypogammaglobulinemia. 



-li- 
lt really means, in practical terms, an inability to produce antibodies in 
adequate quantities. It has been known only for a few years, because in 
the days before antibiotics persons with this condition died of infection 
before the underlying reason was discovered. In the particular patient 
referred to here, lymph tissue from a normal sister was transplanted 
into the patient. For more than five months this tissue produced anti- 
bodies in the patient, and enabled her both to ward off infection and to 
respond normally to vaccines. The very fact that she did not make anti- 
bodies herself enabled the foreign tissue to survive; in a normal person 
antibodies would have destroyed it in a week or two. 

Allergy 
Response to antigens of various kinds — vaccines, serums, micro- 
organisms, plant pollens, animal dander, food, and others, varies greatly 
among individuals, The hypogammaglobulinomic is one extreme -- he fails 
to respond at all, and hence is the victim of an endless succession of 
infections. At the other pole is the allergic person, who responds so 
violently that he is made ill by the mechanism of the response itself. 
During the current fiscal year, our new program on allergy and related 
aspects of immunology has gotten under way with funds supplied by the 
Congress for fiscal year 1957. Support has been given to about one 
hundred projects primarily directed to these problems, at a cost of 
about one and one-third million dollars. At Bethesda, Dr. Jules Freund, 
a distinguished scientist of international renown, has accepted the 
responsibility of recruiting a scientific staff and giving further 1 impetus 
to the program of research in allergy and immunology. The funds requested 



- 12 - 

for fiscal year 1958 will permit this program to move forward. Scientists 
already in the Institute who have interest and competence in this area of 
research are directing their efforts toward emphasis on this new aspect 
of our program. 

Antibiotic Resistanc e 

An instance of abnormal host response to infection which is 
attracting increasing notice is the condition known as fibrocystic 
disease. This is an inherited condition in which there is malfunction 
cf the pancreas, and chronic lung disease. These patients are peculiarly 
susceptible to infection, especially with staphylococci. The antibiotics 
have made it possible to save many of them, at least for a time, but the 
condition still carries a high fatality. The problem of susceptibility 
to infection with staphylococcus and its underlying cause are of funda- 
mental interest. They are also of immediate practical importance as an 
example of resistance of this organism to antibiotics. This is giving 
increasing concern to physicians because many strains of staphylococci 
ire developing which seem highly resistant to antibiotics. An investi- 
gator supported by an NIAID grant has recently shown how the use of 
antibiotics on a hospital ward caused the development of a reservoir of 
drug-resistant staphylococci in the, hospital environment. These resis- 
tant strains are sometimes highly virulent and difficult to control. 

Plasmapheresis 

One project supported by a research grant which has intriguing 
possibilities in regard to production of antiserums is based on a procedure 



- 13 - 

called plasmapheresis. This means that blood is removed from a donor 
and separated into two parts: the liquid and the cells. The latter 
are put back into the patient's veins; the fluid is available for trans- 
fusion or other use. i/hen whole blood is taken from the donor, it is 
generally considered that five pints a year is all he should give, vtfith 
plasmapheresis, volunteers are now giving 26 pints a year, and it is 
probable that this could be doubled -- a pint a week — with no harm to 
the donor. Some of the volunteer donors have been given vaccines to 
make them immune to certain infections; these individuals develop potent 
antibodies which can then be used to treat sick persons. Here is a pos- 
sible means for making antibodies in human serum, instead of using horses 
and other animals whose serums cause annoying and sometimes dangerous 
reactions in patients treated with them. 

Germ-free Animal s 
Increasing interest .- Scientists are becoming impressed with 
the importance of germ-free animals in contributing to our understanding 
of how various microorganisms react with one another in affecting the 
animals which harbor them. The use of animals which are entirely free 
of germs was pioneered some years ago at the University of Notre Dame 
(Lobund), and the group there continue to play a leading role in this 
field of research. In addition to contributing to the Lobund enterprise 
by grants-in-aid, the National Institute of Allergy and Infectious Diseases 
is currently developing a program of research in germ-free animals at 
Bethesda. Equipment has been installed, and staff members trained at 
Lobund are at work in the Bethesda laboratories ♦ 



- Ik - 

Amebiasis .- One of our scientists has been at Lobund for several 
years , and collaborative research by him and members of the Lobund staff 
has revealed the critical importance which bacteria play in the production 
of disease in guinea pigs by the protozoan parasite, Endamoba histolytica . 
Recently, it has been shown that germ-free animals are free of their 
common parasites (protozoa and worms) as well as of bacteria, except that 
certain parasitic worms of dogs have survived the germ- free techniques, 
it is anticipated that the germ-free studies will continue to improve our 
understanding of the diseases caused by parasites of this sort; 

Parasitic worms .- An example of progress now being made in respect 
to the parasitic worms is the recent cultivation of a nematode, Nippostrongylu .' 
muris, in artificial media through its entire life cycle. Normally, the 
larva of this worm invades the skin of the rat, and migrates to the lungs. 
Aftir certain developmental changes there, the worm enters the rat's small 
intestine, where it becomes an adult. Then it lays eggs, which pass out 
of the host to start a new cycle. All of this has now been done by keeping 
the worms under proper conditions in the laboratory, without use of the rat 
or any host animal. As with the viruses, studies of this sort enable 
scientists to understand how disease-producing microorganisms maintain 
their existence, and how their damage may be prevented. The acquisition 
of capabilities for germ-free research will aid in these investigations. 

Schistosomiasis Control 

One of the most serious and widespread of parasitic diseases — 
schistosomiasis -- is caused by worms. There are perhaps 110,000,000 
cases of this disease in the world, many of them in countries where the 



- 15 - 

United States has vital interests. Infections with this parasite are 
prolonged and difficult to cure. Our scientists have recently demonstrated 
that striking reduction in the hazard of schistosomiasis can be achieved 
by chemical destruction of the snails which carry the worms. Under field 
conditions in an area where nearly $0 per cent of children were found 
infected on a single survey, a 79 per cent reduction in snails was accom- 
plished by a single application of sodium pentachlorophenate, a compound 
produced easily and cheaply in the United States and abroad. Completely 
satisfactory results in terms of snail eradication followed one or two 
applications a year. It is too soon to expect definite results regarding 
human cases of disease, but an early downward trend has been observed. 

Other Tropical Diseases 
Diseases of the tropics are of importance to the United States 
because of our numerous commercial and political ties with tropical 
countries, and because of the ever-present possibility that dangerous 
diseases may be introduced into our continental domain. Increased emphasis 
is being placed on this area of research within the National Institute of 
Allergy and Infectious Diseases, with special attention to the numerous 
viruses that are indigenous to the tropical regions. Current emphasis 
is on Central America; since this is the region contiguous to our borders 
it presents the greatest potential hazard to us. The northward progression 
of yellow fever toward Mexico is of special concern, and indicates that 
other viruses transmitted by mosquitoes and other insects must receive 
our serious attention. 



- 16 - 

Training of Scientist s 

One of the most acute needs in our area of responsibility is thai 
for additional highly qualified scientists. Many of our most brilliant 
youngsters are being lost to research when, with proper stimulation and 
support, they could be induced to develop their valuable capabilities. 
This Institute has never been able to make a significant contribution to 
the solution of this problem, and funds are requested for fiscal year 1958 
to enable us to begin a program of training grants. Our Council has 
strongly urged that this program be begun as soon as possible. All 
students of scientific manpower have emphasized the importance and 
urgency of developing on a nationwide basis our scientific researoh 
potential much more fully and rapidly than we have been doing. It is 
hard to imagine an investment that would be sounder than this. 

Gorgas Memorial Laboratory 

The Gorgas Memorial Laboratory is the operating research agency 
of the Gorgas Memorial Institute of Tropical and Preventive Medicine, Inc., 
and is located in Panama City, Republic of Panama. An act (H.R. 8128) to 
authorize a permanent annual appropriation up to hj>150,000 for the main- 
tenance and operation of the Gorgas Memorial Laboratory was passed by the 
United States Government in May 1928. 

The Laboratory has been in continuous operation since 1929 and has 
functioned solely as a research institution dealing with tropical diseases 
and their prevention. In the twenty-six years of research activity the 
Laboratory has contributed materially to the advances in the field of 
tropical and preventive medicine. 



- 17 - 

In addition to the work carried on by the resident staff of the 
Laboratory, visiting scientists have been afforded the opportunity and 
facilities for research. 

It is projected that the funds for fiscal year 1958 will be 
utilized for research on tropical viruses, parasitic diseases, and 
fundamental problems related to them. 

Among the diseases caused by viruses, yellow fever is most 
important, since it has been advancing northward through Central America 
for several years and is a definite threat to the continental United 
States. Many other viruses indigenous to the tropics have been identified 
in recent years, and their role in production of human illness must be 
defined. 

Long-term studies on malaria, leishmaniasis and trypanosomiasis 
receive the chief emphasis among the parasitic diseases. All are impor- 
tant in much of Latin America. Another parasitic disease, toxoplasmosis, 
exists in all the Americas, including the United States, and is receiving 
increasing attention. 

Fundamental research includes investigation of animal and insect 
reservoirs of the viruses and parasites, which are transmitted from or 
by them to man. A great deal of information on the tropical environment, 
its animal and human inhabitants, and their inter-relationships is being 
obtained. 

Summary 

During the current century there has been great progress in the 
control of a number of diseases caused by the animal parasites, e.g. 
malaria, leishmaniasis, amebiasis. These are ordinarily spoken of as 



- 18 - 

"tropical diseases," though none of them is limited to tropical regions. 
But little has been achieved in regard to a large group of ill-defined 
fevers common in the tropics, caused by a variety of viruses, many of 
which have been discovered quite recently. Another virus disease of the 
tropics, yellow fever, formerly regarded as almost "conquered," has again 
become a threat to the United States by moving northward through Central 
America and into the Caribbean. Most of the parasitic and virus tropical 
diseases are transmitted by arthropods (insects, ticks, mites), mosquitoes 
being especially important. 

It is important that further research on these tropical diseases 
be developed. There is always a danger that some of them — particularly 
the viruses — may initiate epidemics in the United States, and in their 
native tropical habitat all are a constant menace to our citizens who 
travel to those areas for business, military, and other reasons. Teams 
of scientists, including virologists, entomologists, and parasitologists, 
must be organized and supported both to extend our knowledge of these 
diseases and to avoid the danger of losing our scientific competence just 
at a time when we are most likely to need it. Plans for a more vigorous 
approach to this problem are included in our FY 1958 program. 

Research progress in allergy and infectious diseases continues to 
be gratifying. Many studies are intriguing in their promise of continued 
and greater achievements for the future. No one can foresee exactly what 
discoveries will be made at cany given time in the future, nor accurately 
predict which projects or even major areas of investigation will be most 
productive. There is only one wav in which it has ever been possible to 



- 19 - 

advance scientific knowledge $ that has been to give; adequate support to 
those who have basic competence, imagination, and incentive. As a 
corollary, it is essential that the number of persons who have these 
qualifications must be not only maintained, but increased. This moans 
that we must help to produce scientists as well as help them fulfill 
their own productive potentials after they have entered the field. We 
shall never know all that we need to know. No matter how much we have 
accomplished, there is infinitely more that remains to be done in all 
fields of health and medicine. 

Changes in 1958 
The increases in obligations proposed for 1958 amount to 
■-. ; 3,?0li,000. It is anticipated that they will be used as follows: 

(a) 0650, 000 for the initiation of a training program. The 
initiation of this program is of paramount importance because of the 
acute shortage of highly trained scientists in our area of responsibility. 

(b) Research Grants — An increase of m>2, 612,000 permits the 
activation of ^21^,000 worth of grants recommended for approval by the 
November Council and permits ol,281i,000 for expansion in the areas of 
allergy and immunology, virology, and tropical medicine (including 
parasitology and mycology) . It further provides for anticipated increased 
overhead amounting to ,701,000 and 3>3>000 additional support for the 
Gorgas i'lemorial Laboratory. 

(c) Direct Operations — The increase requested for direct opera- 
tions ia w6 Ii2, 000. Of this, .,227,700 is available for the expansion of 
the research program. It will provide for 23 new positions which will 



- 20 - 

be allocated among the research projects on germ- free animals, allergy, 
and virology. 

The remainder of the increase will be for additional support 
of services performed on a centralized basis (vl97,100), retirement 
and social security ( .i>lli5,300), annualization of current operations 
(1)61,200), and for cost of regular pay above 52-week base ( tylO , 700 ) . 



Summary of Opening Statement 
by 
Director, National Institute of Neurological Diseases and Blindness 

Public Health Service 
COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
"Neurology and Blindness Activities, Public Health Service" 

The past year has been one of many advances in the Institute's overall 
research attack against the neurological and sensory disorders which today 
afflict some 20,000,000 Americans. There were important specific achievements at 
both the clinical and basic research levels. The extramural research program 
was greatly expanded as was the graduate training grants program. Of major 
significance was the beginning of a shift in emphasis from concentration upon 
specific projects dealing with individual diseases to broad, collaborative field 
investigations, each of them directed to a wide spectra of related disorders. 

Specific research developments during the year included the following: 
A new diagnostic method for the early detection and treatment of a virulent 
form of uveitis, a blinding disease; discovery and tracing of a group of 
nerve fibers connecting the brain with the inner ear, thus providing the 
first definite evidence that hearing is determined not only by external 
stimuli but also by stimuli from the brain itself; a new diagnostic technique 
which makes possible the detection and localization of the great majority 
of brain tumors without opening the skull; and the finding and commencement of 
testing of two promising new chemical compounds directed to control of epileptic 
seizures. 

The extramural research grants program saw an estimated $9,130,000 
awarded in support of 690 research projects,. This compares with 414 grants 
totalling $4,350,000 in fiscal 1956. Research projects are currently under- 
way in institutions in 41 of 48 States and in Puerto Rico. 



- 2 



Graduate training grants during fiscal 1957 will total about 120, the 
award amount being an estimated $3,250,000. This compares with 86 grants 
totalling $1,525,000 during 1956. The same pattern of expansion is reflected 
in the awarding of clinical traineeships and research fellowships. Though 
the extramural training program is only in its third full year, 148 
specialists have already completed their training with the help of grants 
made available under that program. 

During the current fiscal year, collaborative field investigations-- 
in which the Institute plays a central, coordinating role—were launched in 
the following areas among others: Perinatal period (the year from one 
month following conception to one month after birth) factors bearing upon 
cerebral palsy, mental retardation, epilepsy and related disorders; the 
cerebral vascular disorders; the aftermaths of infectious neurological 
diseases; and the impact of the aging process on the nervous system. The 
Institute is currently participating in more than 30 collaborative or 
cooperative research investigations. 



OPENING STATEMENT 
by 
Director, National Institute of Neurological Diseases and Blindness 

Public Health Service 
COMMITTEE ON APPROPRIATIONS 
1958 ESTIMATE 
"Neurology and Blindness Activities, Public Health Service 

Mr. Chairman, Members of the Committee: 

Last year before this Committee, I had the honor to report on the 
research gains of the National Institute of Neurological Diseases and 
Blindness in its first full-fledged attack against the crippling neurological 
and sensory disorders. These include more than 200 diseases. They affect 
about 20 million Americans. 

When this Institute was formed, there were those who believed that a 
research attack upon neurological and sensory disorders was premature, and 
that the Institute could do little to activate productive research on these 
obscure and baffling conditions. The course of events has proved this view 
wrong. The judgment of Congress has been demonstrated. We in the Institute 
have felt a deep sense of responsibility to use the opportunity presented by 
Congressional action to advance every phase of the attack upon these disorders. 

The sequence of events over the years has followed a broad strategic 
plan worked out with a group of scientific and lay advisors of the highest 
caliber. Thus far we have been able to deal effectively with one of the 
most complex and delicate problems in science. This is the mounting of a 
planned attack on disease without reducing the essential freedom of the 
individual investigator. 

This has been a most stimulating experience for all of us in the 
Institute and for our advisors, and I should like to sketch the story 
briefly. Then, I should like to note the state of research in some 



- 2 - 

important areas, including those in which we have grounds for considerable 
optimism and also those in which the ultimate goal continues to seem remote- 

Before discussing the progress in 1957 and the budget proposal for 
1958, permit me to sketch the Institute's program and budget history. 

PROGRAM HISTORY 

In August, 1950, Congress authorized the establishment of the National 
Institute of Neurological Diseases and Blindness, the youngest of the National 
Institutes of Health. The period from 1952, when the Institute was first acti- 
vated with an appropriation of $1,250,000, to 1954, when it received its first 
direct appropriation of $4,500,000, was a period of planning and staffing., 

The period from fiscal 1954 to 1956, when the appropriation was increased 
to $9,861,000, was one of attack on specific vulnerable areas in the field of 
neurological and sensory disorders- -an attack which opened new vistas of 
knowledge in brain surgery, in the biochemical basis of epilepsy, in regenera- 
tion of central nervous tissue, and in other basic problems confronting neuro- 
logical scientists,, This same period witnessed the Institute's successful organ- 
ization of cooperative and collaborative projects which produced an effective pre- 
ventive for retrolental fibroplasia, the then most common cause of blindness in 
infantSo The Institute also achieved better understanding of the nature and preva- 
lence of multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease)- 
problems which must be resolved before a fundamental research attack can be mounted,, 

The 1954-56 period was one in which--for the first time — there was an 
opportunity to launch a realistic training grants program in order to increase the 
number of neurologists, ophthalmologists, and laboratory scientists, the shortage 



- 3 - 

of which was threatening the Institute's promising potential for developing a 
truly National program The period was also characterized by special emphasis 
and support by the Congress of particularly neglected areas under the Institute' s 
research responsibility, notably, cerebral palsy and mental retardation. Finally, 
during 1954-56, the Institute developed projects calculated to implement previous 
findings such as testing the effectiveness of glutamine and asparagine in the 
control of epileptic seizures. 

From the beginning of fiscal year 1957, when the Congress appropriated 
$18,650,000, until today, the Institute has continued to pursue the promising 
research leads which its scientists had previously uncovered in epilepsy, 
cerebral palsy, mental retardation and multiple sclerosis,, In addition, the Insti- 
tute has implemented certain other parts of its program which received special 
attention from this Committee and the Congress. It has enlarged toward full 
potential its graduate training grants program, initiated a promising research 
program in hearing disabilities, and activated its plan for long-term collabora- 
tive field investigation projects. 

As I stated to you last year, in these long-term collaborative field 
investigation projects, the Institute serves as a central laboratory and coordina- 
tion center for studies which require the collaboration of many institutions 
and many scientific disciplines, both clinical and basic. The first collabora- 
tive field investigations, organized in fiscal year 1957, were directed toward 
those crippling conditions--cerebral palsy, mental retardation, epilepsy, and 
certain forms of deafness andi blindness--which arise in infancy and early childhood 
as the result of adverse biological factors (mostly unknown) that operate before, 
during, or shortly after birth (the perinatal period). It is expected that the 
collaborative field investigations of perinatal morbidity, to which I shall refer 
in more detail later, will provide the basic knowledge which is necessary before we 






- 4 - 

can seek effective treatment or prevention of many types of cerebral palsy, mental 
retardation, and other tragic aftermaths of the perinatal period. 

In the development of its new programs for fiscal year 1957, the National 
Institute of Neurological Diseases and Blindness has had the benefit of expert 
counsel from professional leaders and societies throughout the world. We have 
also had the interest and support of the many fine voluntary health organizations 
dedicated to the welfare of neurological patients. Through the National 
Committee for Research in Neurological Disorders, the Institute has continued 
its close liaison with constituent members: United Cerebral Palsy, the National 
Multiple Sclerosis Society, National Epilepsy League, Muscular Dystrophy Associations 
of America, the National Society for Crippled Children and Adults, National 
Association for Retarded Children, Society for the Aid of Crippled Children, and 
the National Foundation for Infantile Paralysis. 

In reviewing the Institute's program trends in fiscal year 1957, it is 
logical to proceed into a consideration of sound program policy and needs for fiscal 
year 1958, Since 1952 there has been a gradual shift of emphasis from the 
specific to the more general type of research attack-from a narrow to a broader 
program design. First, there was the "tooling up" for a pin-pointed research 
attack on specific vulnerable areas; then the attack and its rewards. Next came 
badly-needed support for specific projects which eventually evolved into support 
for wider spectra of disease and, in 1957, rose to a peak in the broad collabora- 
tive projects on the early life cycle of man, the perinatal period. 

In view of this evolutionary process, it is my feeling that 1958 is a 
critical period in which we should pause, take stock and consolidate our broader 
program gains while retaining that flexibility which permits the pursuit of 
specific breakthroughs when and where they occur. 



- 5 - 
I shall develop this theme further, but first allow me to review briefly 
some of the Institute's achievements during the past year. These may best 
be presented by relating them specifically to disease categories. 

Cerebral Palsy 
The condition which most of us label as cerebral palsy has been attributed 
to numerous causes, among them hereditary factors, malformation of the brain, 
disease or injury to the mother, prematurity, deprivation of oxygen (anoxia), and 
mechanical injury at birth. 



- 6 - 

In one type of cerebral palsy, kernicterus, we have managed to relate the 
disease specifically to blood incompatibility (the Rh factor) and--to a considerable 
extent—the disease in newborn babies can now be prevented by multiple transfusions. 

During the past year, some important clues as to the relationship between 
anoxia (lack of oxygen) and cerebral palsy have been developed in experiments with 
guinea pigs which were asphyxiated, resuscitated and observed. A close correlation 
was found between the degree of asphyxia and the severity of the neuromuscular 
damage once the guinea pigs were resuscitated. In previous experiments, it had 
been established that, following their resuscitation, the guinea pigs underwent a 
series of twitchings of the muscles of the face and limbs not unlike the overt 
symptoms of cerebral palsy in humans. 

On the clinical side, efforts to relate cerebral palsy in humans to the 
biologic state of the mother during pregnancy are going forward both at the Insti- 
tute and through various grantee projects. One Institute scientist, on the basis 
of a study of 43 aborted embryos with cerebral abnormalities, has been able to 
determine- => in more than half of the 43 cases studied" -that the abnormalities were 
positively or probably associated with the clinical state of the mother during 
pregnancy. The establishment of the relationship is of considerable importance. 

Last year, Congress made available funds for the launching of a planned 
experimental program using the rhesus monkey. The rhesus monkey lends itself 
particularly well to studies in the cerebral palsy, mental retardation and allied 
disease areas. It is easier to get a brain wave recording from a monkey than from 
a rat or a guinea pig. Further, a baby rhesus monkey can learn certain problems 
when it is five days old and can then be tested for deficits in learning ability 
caused by adverse factors deliberately induced during the prenatal period — factors 






such as nutritional deficiencies and infections. 

The experimental program involving rhesus monkeys is now underway. A 
laboratory of perinatal physiology has been established in Puerto Rico in 
collaboration with the University of Puerto Rico and a free-range colony of 
monkeys has been acquired on an offshore island. 

Mental Retardation 

An estimated 4,500,000 Americans — 1,500,000 of them children--are 
mentally retarded. Five to ten percent of these people are institutionalized 
at an estimated cost to the community of $50,000 per individual over that 
individual's lifetime. Through its own research efforts and through those of 
grantees, the Institute is probing the problems of cause, prevention and cure 
or amelioration. This, we must say, is an area where progress to date has been 
slow. But such progress as has been made augurs genuine hope for significant 
findings that will help alleviate mental retardation in the future. 

Laboratory experiments with guinea pigs and the pending experiments 
with rhesus monkeys mentioned in conjunction with cerebral palsy also bear 
on the problems of retardation. Lack of oxygen (anoxia) has definitely been 
shown to have a retarding effect upon the guinea pigs and on other animals. 
As the monkey experiments get underway, the effects of induced retardation 
will be carefully studied and various drugs will be used to determine their 
impact on these effects. 



- 8 - 

The guinea pig experiments have also led to the development of a 
new (with guinea pigs) technique for applying scalp electrodes. The 
technique, which involves affixing the electrodes to the surface of the 
skull through the use of an adhesive substance, makes it possible to 
secure effective brain wave recordings without subjecting the animals 
to anesthesia for electrode-implanting purposes. Further, the technique 
allows the recording of brain waves over a sustained period of time with- 
out in any way adversely affecting the animal through the recording process. 

Previously-used methods saw the electrodes implanted within the guinea 
pig brain and were therefore not nearly as -effective from the research point 
of view. 

Multiple Sclerosis and Other Demyelinating Diseases 

Multiple sclerosis and related demyelinating diseases afflict many 
thousands of people in this country. A long-term disease, multiple sclerosis 
is extremely difficult to detect in its early stages . Relatively little is 
known about the specific manner in which the disease progresses. The 
disease attacks the various parts of the central nervous system through a 
process known as demyr. -ination in which myelin (a fatty sheath which covers 
the nerve fibers in healthy individuals) disintegrates or fails to regenerate. 

In later stages, multiple sclerosis produces symptoms ranging 
from weakness or paralysis of the parts immediately served by the nerves 
of the brain or spinal cord which have been demyelinated to double 
vision, tremor, difficulties in articulation, and occasional emotional 
disturbances . Several drugs which it was thought held some 



- 9 - 

promise for treating the disease have been carefully tested and found to be of 
little value. There is no known cure. 

However, over the past several years steady progress has been made by 
Institute scientists and by investigacors working on grants from the Institute or 
under other grant programs. This progress has been in basic research directed 
primarily to discovering the nature and structure of myelin, the forces or sub- 
stances which regulate its growth and existence, and the manner in which it 
deteriorates 

An important breakthrough in the attack against multiple sclerosis came in 
1955 when an Institute grantee, using the electron microscope, discovered that the 
myelin sheath of peripheral nerves (as opposed to nerves of the brain and spinal 
cord area) developed as the result of a spiralling of the membranes of certain 
satellite cells around the nerve—cells known as Schwann cells. This clue led to 
development of the idea that satellite cells of the central nervous system, known 
as neuroglia, play an important role in the formation and sustenance of the myelin 
sheath surrounding the nerve fibers of the spinal cord and the brain. 

Last March, the Institute arranged a conf erence- -attended by the world's 
leading authorities on neuroglia--for the purpose of devising ways and means of 
exploiting the research breakthroughs I have just mentioned. That conference has 
since borne fruit. Specifically, an investigator in St. Louis has since demon- 
strated conclusively that myelin in the central ner jus system originates from the 
neuroglia specifically known as the oligodendroglial cells. Another investigator, 
an Institute grantee, has developed a method for producing in experimental animals 
lesions in myelin similar to those which occur in multiple sclerosis. 



- 10 - 

Muscular Dystrophy and Neuromuscular Disorders 

Over the past several years, the Institute has concentrated heavily on 
research into disorders involving muscle or the nerve-muscle junction. Muscular 
dystrophy, a crippling and killing disease characterized by wastage of muscle, is 
an ailment for which there is no known cure. Myositis is a related disease directly 
involving the muscle. Myasthenia gravis, a problem of the nerve-muscle junction, 
involves a failure of impulse transmission at that junction. Unlike dystrophy and 
myositis, this last disorder iss iceptible to treatment and control in many cases 
though, once again, there is no known cure. 

Because we still know relatively little about muscular dystrophy and neuro- 
muscular disorders, our primary research efforts in relation to these disorders 
have been directed to learning everything possible about nerve and nerve-muscle 
transmission and about the electrical, chemical and other influences which play 
a role in that transmission,, During the past year, there have been a number 
of developments in this regard at the Institute which we feel are quite promising. 
I should like to cite some of them„ 

Institute scientists have developed a means of detecting and accurately 
measuring acetylcholine, a chemical substance essential to the transmission of 
impulses between nerve and muscle. Acetylcholine, when associated with another 
compound (tetra-phenyl-diboronoxide) , gives off fluorescence which is, in turn, 
measured by an electronic device. The new technique makes it possible to detect 
and measure minute quantities of acetylcholine in the nerve. 

Working with a ganglion (nerve system) of a squid, one Institute scientist 
has developed an ingenious micro-electrode recording technique. Using equipment 
capable of recording electrical impulses of millionths of a volt lasting for 



- 11 - 

millionths of a second, this investigator has actually probed the synapse area in 
the squid ganglion--that is, the almost infinitesimal space in which one nerve 
transmits impulses to another. 

In concluding this section, I should like to note that this new micro-electrode 
recording technique will — in the next year--be used for recording impulses at the 
nerve-muscle junction in patients with myasthenia gravis. And this, of course, is 
an excellent example of how rapidly research developments at the basic laboratory 
level can be adapted to clinical needs. 

Epilepsy 

Epilepsy represents a problem of tragic proportions, the psychological, 
social andeeconomic consequences of which are--in many respects- -more devastating 
than the seizures. All too often, the epileptic finds himself shunned by his 
neighbors and refused employment he is qualified to hold. 

Epilepsy is not a disease in the conventional sense. It is a manifesta- 
tion of abnormally-discharging brain cells which is apparent only at the time of 
a seizure and which handicaps otherwise normal individuals at that time. Only a 
small percentage of epileptics with extensive brain damage are mentally retarded 
or in any way affected in mental function. 

A highly significant finding of the past year is the tracing of certain 
complex seizure patterns to specific and localized areas of the human brain. Pre- 
viously, these particular patterns could only be described. The significance of 
the discovery lies in the possibility that the seizure patterns in question may 
now lend themselves to effective therapy or surgical intervention once their 
localization has been adequately pinpointed. 

Careful, around-the-clock observation of patients at the Clinical Center 



- 12 - 

has revealed a specific sequence of events during spontaneous seizures based 
upon temporal lobe epilepsy. This detailed observation of spontaneous seizures 
provides additional accurate data as to the seizure pattern and also makes 
it possible to relate the specific bodily movements involved more precisely 
to the brain areas controlling such movements. The establishment of such pre- 
cise relationships is of value both in the treatment of epilepsy and in increas- 
ing our overall understanding of brain function--an understanding vital to the 
development of preventives and therapies for dealing with all neurological 
disorders involving the central nervous system. 

The impact of hypothermia on epileptic discharges was studied during the 
year and the available evidence indicates that cold slows down the electrical 
discharge (firing) of brain cells. Furthermore, hypothermia has proved useful 
in the removal of brain tumors and other brain operations, particularly when the 
person undergoing surgery is in a weakened condition. 

I should like to say a few words about our experiments with chemicals 
designed to control or reduce epileptic seizures. You will recall that Insti- 
tute scientists discovered several years ago that one vital chemical (glutamic 
acid) does not form in sufficient quantity in the brain cells of epileptics, and 
that another chemical (acetylcholine) does not form in sufficient quantity in 
reserve. 

Initially, we sought to correct this chemical deficiency through admin- 
istration to epileptic patients of two substances known as glutamine and 
asparagine. These have now been tested with extreme care, and while they have 
been found to be effective in reducing or controlling epileptic seizures in 
many of the persons to whom they have been administered, they have also had 



- 13 - 
adverse reactions in some cases and annoying side-effects in others. 

The Institute has therefore shifted to experimentation with two other 
drugs--gamma-amino-butyrate and 2-pyrrolidinome--and preliminary results with 
these drugs are encouraging. Both substances have been found to reverse seizures 
in cats and the addition of either to tissue taken from human epileptic brains 
causes a revision of the brain tissue to normal insofar as glutamine and glu- 
tamic acid are concerned. 

Parkinson's Disease 

Parkinson's disease- -sometimes known as the "Shaking Palsy"--is a slow, 
progressive disabling illness which strikes at the brain stem nerve system and 
is characterized by muscular rigidity, bodily tremors, slowness of move- 
ments, sleepiness, abnormal postures and loss of normally automatic movements. 
There is no known cure for the disorder. 

The Institute took an important step forward against the disorder during 
the past year with the creation of conditions in monkeys which closely resemble 
the clinical signs of Parkinsonism in humans. The administration of the drug 
reserpine daily over long periods of time has produced in these animals 
tremor, rigidity, and other Parkinson-like symptoms. We have also found that 
these Parkinson-like symptoms can be diminished or abolished by injection of 
an anesthetic into the brain ganglia known as the globus pallidus and ansa 
lenticularis. 

Reserpine, it should be noted, is widely used in the treatment of 
emotionally disturbed humans. Animal studies involving use of reserpine have 
shed considerable light on means of coping with the side-effects the drug has 
been found to produce in people being treated with it. For these side-effects 
are Parkinson-like symptoms not unlike those produced in animals. It is there- 
fore of interest to record that — only a few months ago--an investigator 



- Ik - 

using reserpine in the treatment of patients developed a drug which eliminates 
or reduces the Parkinson symptoms in those undergoing such treatment. 

Brain Tumors 

During the past year, there have been several technical advances of 
promise in the field of "brain surgery. One of these is a technique developed 
by Institute scientists for the detection and localization of brain tumors. 
The technique, which makes use of the isotopic tracer method coupled with 
electronic devices, has been shown to be 80 percent effective and efforts 
are already underway to increase its effectiveness. 

A second development, still at the animal experimental level, 
involves the use of ultra-sound for surgical purposes. Experiments in 
this area are being carried on by an Institute grantee at the University 
of Chicago. The grantee reports that he has developed ultra ionic equip- 
ment and techniques whereby high frequency sound waves may be used to 
excise tumors and diseased areas deep in the animal brain and not noi nally 
susceptible to surgery by knife. The grantee has reported that he has 
produced both small and large lesions in animal brains with extreme 
precision without any damage whatsoever to the healthy brain tissue 
in the path of the sound waves. 

The grantee believes that he is on the threshold of making the 
ultra- sonic technique applicable to human surgery. The Institute is 
watching his progress with a great deal of interest. 

Eye Research 
Today, there are about 320,000 blind persons in our country, and an 
estimated 27,000 will go blind during the next twelve months—about half of them 



- 15 - 

blinded by disease. Glaucoma, uveitis, retrolental fibroplasia, diabetic 
retinopathy, cataract, tumerous growths-- these have hitherto been among the 
major blinding diseases, and mosc of them continue to wreak havoc upon the 
human eye. 

You may recall my comments last year relative to retrolental fibroplasia 
in which I pointed out that this disease, which once blinded thousands of pre- 
mature infants yearly, was well on its way toward conquest as the result of 
collaborative research involving the Institute and 75 outside investigators 
in 18 different hospitals. 

I can now report that--as the result of these research findings and the 
cooperation of physicians and hospitals throughout the country--retrolental 
fibroplasia as an active disease is rapidly disappearing. A recent survey of 
New York City hospitals, for example, revealed that the number of premature 
babies blinded by the disease had dropped 78 percent in one year. The retro- 
lental fibroplasia story is but indicative of how the findings of a specific 
research project can be translated into broad-based collaborative action with 
exceedingly fruitful results. 

During the past year, progress has been made in developing diagnostic 
and treatment techniques for uveitis, a blinding disease caused by tuberculosis, 
syphilis and brucellosis. An Institute scientist has developed a promising new 
test for diagnosis of toxoplasmosis infection, a form of uveitis brought on by 
a parasite. This development, which is still undergoing validation, is expected 
to surpass any known diagnostic method insofar as toxoplasmosis of the eye is 
concerned. Early treatment may thus be instituted and blindness averted. 



- 16 - 

Last year, I reported that the administration of the drugs, pyrimethamine 
and sulfadiazine, provided a cure for uveitis in some cases and tended to keep 
it from progressing further in others „ We are now in the process of evaluating 
a new drug--a steroid compound- -which shows promise of giving even better results 
with less toxic effect upon the patient. 

Institute researchers have continued to concentrate upon glaucoma, the 
dread disease which blinds many thousands every year The testing of various 
types of drugs directed to reducing intra-ocular pressure is going forward,, 
As you know, the increase of this pressure in the eye is the main cause of 
blindness in cases of glaucoma. In this connection, I should like to note 
that we have discovered the existence of a rich nerve supply in an area of the 
eye directly involved in the regulation of intra-ocular pressure. Thr s new 
finding gives us a promising lead to explore in the effort to develop more 
effective treatment and preventive techniques for glaucoma. 

During the past year, Institute scientists — working under the overall 
direction of Dr. Ludwig von Sallmann, one of the world's most eminent ophthal- 
mologists—have fathered a number of electronic developments and allied 
techniques which are directed to early diagnosis and treatment of diseases of 
the retina. Among these advances is one involving the use of electroretinograph. 
This will make it much easier for physicians to distinguish relatively early between 
congenital or hereditary degenerations of the retina on one hand and clinical 
diseases which are very similar in form and d elopment on the other. 
Hearing Research 

Today, there are an estimated 15,000,000 Americans with some kind of 
hearing defect. An estimated 4,500,000 of these are seriously handicapped by 



- 17 - 

deafness and about 760,000 are totally deaf. Yet, in the face of this tremendous 
problem, we must admit that 50 percent of all deafness is either chronic or 
congenital and that, insofar as congenital deafness is concerned, the causes are 
virtually unknown. 

During the past year, the Institute has taken two significant steps 
which hold genuine promise for the future of hearing research. First, we have 
launched an extensive hearing research grant program which I want to discuss in 
more detail later„ Secondly, an Institute scientist has made some key discoveries 
as to the relationship between the ear and the seat of the higher mental functions 
in the brain,, Knowledge in this area is of vast importance if we are to 
understand the basic causes of hearing loss and deafness as well as the cause 
and nature of such complex disorders as aphasia. 

Among these findings was one involving the olivo-cochlear bundle, a 
group of nerve fibers which arise in the lower part of the brain (the medulla) 
and terminate in the cochlea, the tiny organ in the inner ear which translates 
sound waves into nerve impulses. Originally, it was felt that hearing was a 
"one-way" process with outside acoustic stimuli being received and screened 
by the ear and then carried to the upper auditory centers of the brain. In 
short, it was believed that the brain itself exercised no positive or acti- 
vational influence on the hearing process but merely reacted to sound waves 
received from the external environment „ 

The finding of the olivo-cochlear bundle and the tracing of its 
course from brain to inner ear has lead to experiments at the Institute and 
elsewhere which indicate that hearing is determined not only by external 



- 18 - 
stimulus but also by stimulus from the brain itself. What this "feed back" 
mechanism means in specific terms to our understanding of deafness and neuro- 
logical disorders involving the ear awaits further study„ But that it opens 
up broad new vists of research into the nature, cause and treatment of 
these disorders cannot be questioned. 



- 19 - 
GRANT PROGRAMS: RESEARCH AND TRAINING 

The growth and expansion of the Institute's extramural research 
and training programs over the past few years have been gratifying. This, of 
itself, lends support to the thesis that the time has come to think more in 
terms of consolidating our progress to date with more emphasis on the broad 
team attack on related diseases as opposed to the specific project research 
approach. 
The Research Grant Program 

In 1952, the year of the Institute's activation, we awarded 119 
grants totalling $1,015,000 for extramural research. In fiscal 1956, the 
comparable figures were 414 and $4, 350, 000 o During the current fiscal 
year, we are awarding an estimated $9,130,000 in support of 690 research 
projects* This Committee will be interested in knowing that 29 grants 
totalling more than $427,000 have been awarded for hearing research alone, 
a development of some significance in light of the relatively recent start 
made in the hearing research area as a whole. 

The number of institutions participating in the research grant 
program has continued to increase. At present, there are extramural projects 
underway in institutions in 41 of the 48 States and Puerto Rico. Not a few 
of the research developments which I have already brought to your attention 
had their inception in the extramural research program,, 
The Training Program 

Like the research grant program, the training effort has had a 
steady growth and the results to date are most encouraging. The indications 
are that the Institute would be well advised to concentrate upon (1) maintaining 
the existing training level in terms of number of trainees; and (2) fostering 



- 20 - 
the completion of training for those now in process and encouraging their 
entry into research or teaching positions in neurology and related fields. 

Let me present Just a few indications of the progress we have been 
making. Graduate training grants totalled 52 at an investment of $900,000 
in fiscal year 1955* Last year, the comparable figures were 86 and $1,525,000. 
During the current fiscal year, we are awarding an estimated $3,250,000 for 
120 grants. A similar situation prevails insofar as traineeship and fellowship 
awards are concerned. Fellowships, which totalled ^1 at an investment of 
$150,000 in 1956, will this year number 183 totalling an estimated $590, 000 by 
the end of the current fiscal year. 

At present, sixty hospitals, universities and other educational institu- 
tions in 31 states and in Puerto Rico are participating in the training program. 
And — despite the fact that the program is now only in its third full year- 
ly specialists have already completed their training, ikf of them in neurology 
and one in ophthalmology. 

As in the research grant field, the training area has also seen the 
development of interest in hearing. To date, 3 training grants totalling 
$57,Jf64 have been made in the otology field and four others totalling $121,000 
are pending. 

NEW PROGRAM TRENDS ; COLLABORATIVE AND COOPERATIVE FIELD INVESTIGATIONS 

In the first section of this testimony, I summarized the program 
history of the National Institute of Neurological Diseases and Blindness. 
The trend has been from dedication of interest to specific projects or 
individual disease categories to a broader attack on a wider spectrum of 
related neurological and sensory disorders. As I mentioned previously, 



- 21 - 
the most advanced of the programs symbolic of the new trend is to be found in 
the Institute's collaborative attack on perinatal morbidity which concerns 
primarily cerebral palsy, mental retardation, epilepsy, and certain forms of 
deafness and blindness. 

The proposal to inaugurate this type of collaborative field investigation 
was made to this Committee and the Congress last year. 

With the discovery of the effects of German measles in the pregnant 
mother on the newborn and the observation that blood incompatibility between 
the mother and the fetus may produce kernicterus, a malignant form of cerebral 
palsy, the evidence is mounting to incriminate adverse biological factors in 
the perinatal period (from the time of conception to the first month of life) 
as the source of most cases of cerebral palsy and mental retardation. Moreover, 
such adverse biological factors=-in a more lethal form--probably account for 
the many still births and other reproductive failures which in this country 
destroy one-fourth of each succeeding generation before or at the time of 
birth. 

To track down valid leads as to the nature of these noxious perinatal 
factors, it is essential to examine and follow up thousands of pregnant women 
and newly-born infants. Further, it is necessary to do so under uniformly- 
controlled conditions over a period of years. This approach requires the 
active collaboration of many institutions united under a central plan, as 
well as of many clinical disciplines--obstetrics, pediatrics, neurology and 
orthopedic surgery among them. 

Moreover, this collaborative research effort demands the active 
participation of many basic scientists — geneticists, embryologists, anatomists, 
pathologists, chemists, psychologists, and biostatisticians. Finally, experi- 
ments bearing on cerebral palsy and mental retardation now being performed 
in smaller animals must be applied to the higher primates in order to provide 



- 22 - 
an experimental situation more comparable to the situation of human "beings. 
As I noted earlier, the Institute has already begun such a project in the 
monkey colony in Puerto Rico. 

This collaborative field investigations program, a long-range effort, 
is expected to continue for a decade or longer. When in full operation, the 
project will see 12 or more institutions collaborating with tbe National 
Institute of Neurological Diseases and Blindness and some 6,000 persons under 
study. Two institutions, Yale University's School of Medicine and Brown 
University, are already active in the investigation. Yale is carrying on its 
work within its own medical facilities, whereas Brown will be utilizing the 
Meeting Street School, the Providence I^ying-In Hospital, and the Cerebral Palsy 
Clinic of the Rhode Island Hospital. The National Advisory Neurological Diseases 
and Blindness Council, which approved grants of $107,799 and $97,633 to Yale 
and Brown respectively, will review at its March 1957 meeting an additional 
15 new grant applications in this field, in the amount of $1,804,015. 

The collaborative field investigation of perinatal morbidity has 
been associated with a spontaneous growth of interest on the part of the 
country's scientists to initiate cooperative field investigation projects 
in other broad areas of neurological and sensory disorders, notably cerebral 
vascular disease, multiple sclerosis, the aftermaths of infectious neurological 
diseases and the process of aging in the central nervous system. Already 12 
of these projects have been approved in the amount of $288, 3^9* Thirteen 
additional applications in the amount of $312,7^7 sxe pending Council review. 

To summarize, lk awards in the amount of $493 .> 7^1 already have been 
made for collaborative or cooperative field investigations; 30 new applications 
in the amount of $2,116,762 are pending review by the Institute's National 
Advisory Council in March, 1957- 



- 23 - 

In this presentation I have endeavored to show the nature of the 
activities of the National Institute of Neurological Diseases and Blindness 
from 1952 through 1957) the evolutionary shift in its program design to 
breeder and more coordinated objectives j and the continuing productivity 
of its research marching in step with an accelerated program expansion. 

The increases in the 1957 appropriations for neurological research 
were well timed, coming as they did in a period when the Institute program 
was in transition to a broader and more inclusive type of research effort, 
Bnd when there was a rising tide of interest in the training of scientific 
manpower. As a result of the 1957 increases, the entire field of neurological 
and sensory disorders has been vitalized. 

It is estimated that the 1957 increases will be expended during the 
current year, or approximately so, without compromise to the quality of 
research. But perhaps even more important is the fact that the 1957 program 
objectives subscribed to by this Committee and the Congress have been 
realized. To the training program has been added needed momentum. The 
collaborative and cooperative field investigations are in active operation. 
J$ye research has been rounded out, and, for the first time, a truly national 
research and training program in deafness and hearing impairments has begun* 

This brings my statement to plans for 1958 • In view of the changing 
scene of program emphasis from single projects in individual disease categories 
to an increasing, number of team attacks on wide spectra of neurological and 
sensory disorders, it is proposed that our Institute give continued support 
to the collaborative and cooperative field investigations. Also, because 
of the cross-fertilization of the many clinical and scientific disciplines 
required to man these projects, it is proposed that the training programs 



- 24 - 
be maintained at their current levels. 

As I have previously indicated, fiscal year 1958 is a propitious year 
for the consolidation of the Institute's new gains, a e;ar also in which 
there should be some "time out" for sharp directional evaluations. These 
proposals call for a budgetary flexibility if major achievements are to 
be consolidated wherever they occur. 



SIMMARY OF OPENING STATEMENT 
by 
Director, national Institutes of Health 
Public Health Service 

COMMITTEE ON APPROPRIATIONS 
for 
"Grants for Construction of Health Research Facilities, 
Public Health Service" 



Authority . The Health Research Facilities Act of 195& 
authorises grants, to be matched equally by recipient institutions, 
for constructing and equipping research facilities for the 
health sciences, 

Resume of Early Activities „ The members of the National 
Advisory Council on Health Research Facilities were appointed 
and administrative machinery for the program was established 
at NIH. Response to the new program was enthusiastic and 
applications were received from throughout the country. The 
Council recommended and the Surgeon General approved 80 grants 
totalling some 25 million dollars. 

Further Need , By January 15, some 228 institutions had 
applied or indicated interest in applying for construction grants 
totalling over $116,000,000. The need for assistance in the 
construction of research facilities in the health sciences is 
nationwide. It is clear that the available funds under this three- 
year program will provide assistance for only a portion of the 
meritorious applications. It is also clear that matching funds 
are widely available from private or other nonfederal sources. 



At midpoint of the p.vcgrain ! s first year, the Council had 
recommended grants totalling over 85 percent of the funis available 
for the fiscal year = Some 1^0 institutions had formally applied; 
88 had indicated intention to do so ; and more than 320 others 
had requested application forms. 



OPENING STATE! ENT 
by 
Director of national Institutes of Health 
Public Health Service 

COMMITTEE OH APPROPRIATIONS 
1958 ESTIMATE 
for 
"Grants for Construction of Health Research Facilities , 
Public Health Service" 



Mr. Chairman, Members of the Committee: 

AUTHORITY 

The "Health Research Facilities Act of 1956" (Title VII 
of the Public Health Service Act, as amended by Public Lav 835> 
84th Congress), provides for "grants-in-aid to nonfederal public 
and nonprofit institutions for the constructing and equipping of 

facilities for research in the sciences related to health 

medicine, osteopathy, dentistry, and fundamental and applied 
sciences vhen related thereto." 

For this purpose, the Act authorized an appropriation up 
to $30,000,000 for Fiscal Year 1957 and for each of the two suc- 
ceeding fiscal years . In its supplemental appropriations for 
Fiscal Year 1957; the Congress appropriated the amount of 
$30,000,000 for activities under the Act. 

The legislation established the National Advisory Council 
on Health Research Facilities, consisting of twelve appointive 
members and an ex officio member from the National Science 
Foundation, with the Surgeon General of the Public Health Ser- 
vice as Chairman. The Council advises and assists the Surgeon 



- 2 - 

General in policy matters arising in the administration of the 
Act ; aids in preparing general regulations for the program, 
considers all applications for grants, and makes recommenda- 
tions to the Surgeon General with respect to their approval 
and the amount to he granted. The grants, hy the Act's provi- 
sions, are made, upon a basis of not more than 50 percent for 
the Federal share, following submission of a formal application, 
to institutions throughout the country,, and only if recommended 
for approval by the Council. 

The Health Research Facilities Act also provided that 
"on or before January 15, 1957> and annually thereafter, the 
Surgeon General, in consultation with the Council, shall pre- 
pare an annual report and submit it to the President for 
transmission to the Congress, summarizing the activities under 
this title and making such recommendations as he may deem 
appropriate." 

Such a report has been prepared and submitted concern- 
ing this new program during its first five months, from the 
time the bill was signed by the President, on July 30, 19?6, 
through December 31; 1956. The material contained herein is 
to some degree derived from that annual report. However, this 
attachment also furnishes information related more specifically 
to the Fiscal Year 195^ appropriation request for this con- 
struction grant program. 



- 3 - 

RESUME OF EARLY ACTIVI TIES 

The National Advisory Council on Health Research Facili- 
ties was established as soon as possible after the President 
signed the bill into law, the twelve appointees being announced 
on September 10, 1956* Here a clear sign of nationwide reali- 
zation of the new program' s importance was seen, for all of 
the twelve distinguished individuals, from all parts of the 
country, who were asked to undertake this public service, 
gladly accepted the charge. 

The Surgeon General placed administrative responsibility 
for the program with the Public Health Service's research bureau, 
the National Institutes of Health; a Health Research Facilities 
Branch was established in the Institutes' Division of Research 
Grants; and staff were immediately transferred or recruited to 
the Branch to carry out the program. Institutions doing re- 
search in the health sciences throughout the nation were informed 
and advised concerning the program through the press, professional 
journals, special announcements, letters, meetings, and so on. 

The immediate and continuing response has been both en- 
thusiastic and significant--in terms of interest, the nation- 
wide geographic distribution of this interest, the variety of 
types of health science institutions interested, the kinds of 
needs disclosed, and the dimension of these needs. 

Though cognizant of this strong interest, the National 
Advisory Council on Health Research Facilities, at its first 



- k - 

meeting on September 2^-25, 1956, was necessarily occupied 
with discussion of its responsibilities under the Act and 
with advising upon the regulations required for administer- 
ing the Act. Achieving these things, the Council at this 
meeting also considered some 31 applications for research 
construction grants, and recommended seven of the more urgent 
requests. The Surgeon General subsequently approved these 
recommendations, and the applicant institutions are being paid 
the grants. The remaining 2k applications were deferred by 
the Council to permit project- site visits by its members and 
to obtain more adequate information upon broad needs of the 
program throughout the country. 

Some 5^ project-site visits were made by teams of 
Council and NIH staff members in the two-month period between 
September 25 and the second Council meeting on December 3-5« 
At the same time, the Council was studying additional appli- 
cations submitted during this period of time. 

FURTHER ACTION AMD SIZE OF THE NEED 
Requests totaling $66,0*1-6,507 in 129 formal applica- 
tions were before the Council when it met again in December. 
The Council deferred or disapproved 56 applications, for 
$27,102,305. The Council recommended 73 applications in the 
amount of $2l+,M5c,*+67 for payment from Fiscal Year 1957 funds, 
and they were later approved by the Surgeon General. 



A list is appended of these 73 grants and cf the 7 
recommended at the September Council meeting. 

The formal applications, however, represented only a 
partial indication of the need. For the Council also reviewed 
"notices of intention" to submit applications by 89 institu- 
tions in the additional amount of $^-9,l60,774. 

The need for assistance in the construction of research 
facilities in the health sciences are thus demonstrated to be 
nationwide and extensive, although the exact size is as yet 
not completely determined. Since the Council meeting, informa- 
tion has continued to come in to the Health Research Facilities 
Branch. By January 15, 1957, some 1^-0 institutions had formally 
applied and some 88 others had officially indicated their in- 
tention of doing so. The demand for Federal funds by these 228 
institutions is over $116, 600,000. This figure, too, is ex- 
pected to rise significantly because over 320 other institu- 
tions, which have not so far applied or indicated their inten- 
tions, have asked for application forms. At mid-point of the 
program's first year, the Council has recommended grants total- 
ing over 85 percent of the current fiscal year's available funds. 
In recommending these awards, the Council has given careful at- 
tention tc the law's provisions calling for equitable distribu- 
tion, and the awards recommended thereby reflect a wide geo- 
graphic distribution. There is appropriate correlation between 
the grants and such regional factors as population, location of 



- 6 - 

institutions doing or capable of doing research, numbers of 
scientific investigators, and training facilities for the 
health professions. 

In view of the pressing need for construction funds, 
the Council thus far has recommended only such grants as 
would get actual construction started, and deferred until 
later requests for research equipment which could not he in- 
stalled until construction was completed, 

It is clear that the available funds under this three- 
year program will provide assistance for only a portion of 
the meritorious applications. It is also clear that matching 
funds are widely available from private or other nonfederal 
sources as a result of the stimulus provided by the Health 
Research Facilities Act. The Council has scheduled two ad- 
ditional meetings this fiscal year, on March 18-20 and 
May 27-29, when the members will again review projects on 
which action was deferred and review those new applications 
received since the December meeting. 



(Followed by P. 8 et seq: List of Grants. ) 



8 - 



Health Research Facilities Construction Grants 
Recommended and Approved Following 
September and December, 19 5o 
Meeting of the National 
Advisory Council on Health Research Facilities 



INSTITUTION 



FACILITY 



AMOUNT 



ALABAMA 



University of Alabama Clinical research 

Medical Center laboratories: new 6-story 

Birmingham, Ala. research facilities building 



Southern Research 

Institute 
Birmingham,, Ala. 



Medical research laboratory: 
new 5 -story research 
facilities building 



$1,033,500 



250,000 



CALIFORNIA 

Stanford University 
Medical School 
Stanford, California 



Palo Alto Medical 

Research Foundation 
Palo Alto, California 

California Institute 

of Technology 
Pasadena, California 



University of Southern 

California 
Los Angeles, Calif. 



Basic science research $1,500,000 
research building; new 
three -story and basement 
medical research building 

Medical research in health 258,1^5 
and health-related sciences : 
new medical research building 

Basic science laboratory for V/7,000 
medical research: new 3-story 
and basement building for 
biological research 

Medical research laboratories: 85^,500 
new basic medical sciences 
building (^-story) for 
medical school 



COLORADO 



National Jewish HoS' 
pital at Denver 



Colorado A & M College 
Fort Collins, Colorado 



Medical research facilities: $250,000 
new medical research laboratory 
building 

Research facility for animal 96, 000 

diseases and their relation to 

man: new one-story contagious 

disease animal laboratory 

building 



- 9 - 



INSTITUTION 



FACILITY 



AMOUNT 



CONNECTICU T 

Yale University 
School of Medicine 
New Haven, Conn. 



New research laboratories 
for Anatomy and Biochemistry: 
Addition of a 3-story and 
basement research wing to 
Sterling Hall of Medicine 



$k6l,6l2 



DISTRICT' OF COLUMBIA 



Georgetown University 

Washington, D.C. 

Rev. T. Byron Collins, S.J. 



Children's Hospital 
Washington, B.C. 



"Animal Research Laboratories" 



To increase research activities 
and improve the diagnosis and 
treatment of pediatric diseases : 
6th floor addition to existing 
building, and 3d floor addition 
to planned new building 



75,000 



fc)M,6 



oq 



FLORIDA 



University of Miami 
Miami, Florida 



Basic medical research labora- 
tories : new 8-story medical 
science research building 



$9^1,720 



GEORGIA 



Emory University 
School of Medicine 
Emory University, 
Georgia 



Medical research facilities 
for Medical School: remodeling 
and expansion of research lab- 
oratory facilities 



$200,000 



ILLINOIS 



University of Chicago 
Division of Biological 
Sciences 



University of Chicago 
Division of Biological 

Sciences 
Chicago, Illinois 



Medical research laboratories: $250,000 
remodeling of existing isolation 
facility into research labora- 
tories 



Laboratory of Physiological 
Psychology: remodeling of an 
existing building 



$22. 950 



- 10 



INSTITUTION 



FACILITY 



AMOUNT 



ILLINOIS (continued ) 

University of Illinois 
Research Laboratories 
Chicago, Illinois 

University of Illinois 
College of Dentistry 
Chicago, Illinois 

University of Illinois 
Department of Anatomy 
Chicago, Illinois 

University of Illinois 
Dept, of Biological 

Chemistry 
Chicago, Illinois 

University of Illinois 
Medicine -Allergy Unit 
Chicago, Illinois 



Research laboratories for studies $50,000 
in immunology: remodeling of 
present structure 



Dental research facilities : 
remodeling 10th floor of exist- 
ing building 

Basic medical research labora- 
tories : remodeling of anatomy 
laboratories 

Biochemical research laboratories : 
remodeling of existing 
laboratories 



Basic research laboratories for 
allergy research: remodeling of 
existing laboratories 



26,250 



2,600 



8,500 



3^-oo 



INDIANA 



Indiana University 
Psychiatric Research 
Indianapolis , Indiana 



Psychiatric research institute: $ 36, 12 '4 
to provide built-in equipment 
for the Institute of Psychiatric 
Research 



Indiana University 
Bloomington, Indiana 



Research animal care facility: 
a new one -story animal care 
facility 



18,375 



mdiana University 
Indianapolis, Indiana 



Indiana University 
Dental School 
Indianapolis, Indiana 



Medical Science Building: Basic 109,500 
scientific equipment grant for 
research areas of the Medical 
Science Building 

Research and teaching labora- 127 .,283 
tories in dentistry: a new 
5 -story and basement wing on 
Dental Building 



- 11 - 



INSTITUTION 



FACILITY 



AMOUNT 



IOWA 

State University of 

Iowa 
College ©f Dentistry- 
Iowa City, Iowa 

State University of 

Iowa 
College of Medicine 
Iowa City, Iowa 

State University of 

Iowa 
College of Medicine 
Iowa City, Iova 

KENTUCKY 

University of Kentucky 
Lexington, Kentucky 



Dental research facility. $122,500 
2-story research "building (new) 



Animal care facilities for 75*000 
Medical School: remodeling, 
equipping and expanding of 
animal care facilities 

Medical research in Otolaryngol- 20,000 

ogy: remodeling of present 

facilities 



Research laboratories for 
"basic sciences in Medical 
School: new 6-story and base- 
ment medical sciences research 
building 



$1,208,992 



MARYLAND 



Baltimore City 

Hospitals 
Baltimore, Maryland 



Johns Hopkins 
University 
Baltimore, Maryland 



Medical research laboratory: $115*000 
conversion of tuberculosis 
building to a research labora- 
tory building 

Basic science facilities for 9^0,000 
medical research: new 11-story 
and basement research building 



MASSACHUSETTS 



Massachusetts General 

Hospital 
Boston, Mass. 
James C. White, M.D. 

Tufts College (Tufts 

Univ. ) 
Dept. of Biochemistry 
Boston, Mass. 



"Neurosurgical Floor, Warren $ 95jO'+5 
Medical Science Building" 



Research laboratories --Bio- 19,6^-8 
chemistry and Nutrition: remodel- 
ing three existing research 
laboratories 



- 12 - 



INSTITUTION 

MASSACHUSETTS (continued) 

The Boston Dispensary- 
Boston, Mass. 



Mass. General Hospital 
Boston, Mass. 



New England Deaconess 

Hospital 
Boston, Mass. 

Retina Foundation 
30 Chambers Street 
Boston, Mass. 



New England Center 

Hospital 
Boston, Mass. 



Austen Riggs Center, 

Inc. 
Stockridge, Mass. 



Worcester Foundation 
for Experimental 
Biology 

Shrewsbury, Mass. 



FACILITY AMOUNT 



Rehabilitation research lab- $125,000 
oratory: addition of one re- 
search floor to research 
building under construction 

Psychiatric research and teach- 36,503 
ing laboratory: completion of 
an unfinished research lab- 
oratory, 6th floor, Warren 
Building 

Additional space for animal 120,000 
care facilities : addition of 
one floor to existing laboratory 

Basic research laboratory in 300,000 
field of diseases of the eye : 
new basement and 3-story re- 
search building 

Medical science research lab- 1+00,000 
oratory; completion of four un- 
finished floors into research 
laboratories 

Psychiatric research and treat- l80,6V7 
merit : extensive remodeling and 
addition of wings to existing 
building 

Biological and chemical research 2^-1,000 
in the medical sciences : expan- 
sion of animal care facilities 
and remodeling of cancer labora- 
tory facilities 



MICHIGAN 



Wayne State University Medical research laboratories: $900,000 
College of Medicine new 8-story and basement re- 
Detroit, Michigan search wing on present structure 



University of Michigan 
School of Public 

Health 
Ann Arbor, Michigan 



Research facilities for School 
of Public Health: a new research 
laboratory addition to the exist- 
ing structure 



605,000 



- 13 - 



INSTITUTION 

MICHIGAN (continued) 

University of Michigan 
Ann Arbor, Michigan 



University of Michigan 
Ann Arbor, Michigan 



FACILITY AMOUNT 



Medical research facilities: $ 58,522 
remodeling 7th floor of re- 
searcn building 

Mental health research: new 600,000 

structure for research 

laboratories 



MINNESOTA 

University of Minnesota 
Medical School 
Minneapolis, Minn. 
Dr. Harold S. Diehl 

University of Minnesota 
College of Medical 

Sciences 
Minneapolis, Minn. 
Dr. Harold S. Diehl 



"Department of Anatomy Research 26,110 
Facilities; Jackson Hall" 



"Department of Physiological l6l,000 
Chemistry, Physiology, and 
Pharmacology Research 
Facilities --Millard Hall" 



MISSOURI 



University of Kansas 

City 
School of Dentistry 
Kansas City, Missouri 

Washington University 
St. Louis, Missouri 



Washington University 
David P. Wohl, Jr. , 
Memorial Hospital 
St. Louis, Missouri 

NEW YORK 

Cornell University 
Veterinary College 
Ithaca, New York 

Sloan -Kettering Insti- 
tute for Cancer 
Research 

New York, New York 



Dental research: completion of $ ^9*975 
fourth floor of the existing 
dental building 



Basic health sciences laboratory 1^9, 955 
facilities : new 3-story research 
laboratory addition to present 
building 

Medical research laboratories: 71*005 
a 2-story addition to existing 
research building 



Research facilities for disease- $ 75*000 
free animals: new fire -proof 
laboratory building 



Basic science research insti- 
tute in the field of cancer and 
allied diseases : new research 
building of 12 stories, plus 
penthouse 



900,000 



- 1U - 



INSTITUTION 

NEW YORK (continued) 

Roswell Park Memorial 

Institute 
State of New York 
Dept. of Health 
Buffalo, New York 

New York University 
Belle vue Medical 

Center 
New York, New York 

Rockefeller Institute 

for Medical Research 
New York, New York 

Columbia University 
College of Physicians 

& Surgeons 
New York, New York 

University of Buffalo 
School of Medicine 
Buffalo, New York 

Albany Medical College 
of Union University 
Albany, New York 
Harold C, Wiggers 



FACILITY 



AMOUNT 



Basic science research insitute $6^6,000 
in the field of cancer and allied 
diseases : new 7-story basic 
science research building 



Research in clinical medicine : 
remodeling existing laboratories 
in Bellevue Hospital 



75,298 



Basic medical science research: 600,000 
new 9 -story research building of 
reinforced concrete 

Animal care facilities for 366,300 
medical school: remodeling and 
expansion of animal care 
facilities 

Basic science research labora- 1+63,020 

tory; new k -story research 

laboratory 

"Construction of New Animal ^5,000 

Quarters" 



NORTH CAROLINA 



Duke University 
Durham. North Carolina 



Medical research laboratory: 
addition of a new ^-story wing 
to William B. Bell Medical 
Research Building 



$105,000 



OHIO 



University of 

Cincinnati 
College of Medicine 
Cincinnati, Ohio 

Ohio State University 
College of Medicine 
Columbus, Ohio 



Medical research facility: $865,688 
New medical research building 



Medical research facility: 900,000 
new 11-story research laboratory 
addition to existing building 



- 15 - 



INSTITUTION 

OHIO (continued) 

Ohio State University 
College of Dentistry 
Columbus, Ohio 



FACILITY 



AMOUNT 



Dental research laboratories: $290,000 
new research laboratory addition 
to an existing structure 



The Elizabeth Gamble 
Deaconess Home 



"Construction and Equipment of 
Fourth Floor on Institute of 

Association operating Medical Research Euilding" 

the Christ Hospital 



Institute of Medical 

Research 
Cincinnati, Ohio 
L. H. Schmidt 



184,000 



PENNSYLVANIA 

Jefferson Medical Col- 
lege of Philadelphia 
Philadelphia, Pa 5 



Research laboratory for blood $ 24,572 
and plasma fractionation: 
remodeling of second floor of 
existing building into laboratories 



Jefferson Medical Col- Department of Surgery research 

lege of Philadelphia laboratories : remodeling of 
Philadelphia, Pa. portion of 10th floor to provide 

surgical research laboratories 



Jefferson Medical Col- 
lege of Philadelphia 
Philadelphia, Pa. 



Jefferson Medical Col- 
lege of Philadelphia 
Philadelphia, Pa. 



University of Pitts- 
burgh 

Division of Natural 
Sciences 

Pittsburgh, Pa. 

University of Pitts- 
burgh 
Pittsburgh, Pa. 



Basic science research labora- 
tories : remodeling of third 
floor of existing structure into 
research laboratories 



51,883 



Psychiatric research laboratories: 22,235 
remodeling of portion of 10th 
floor to provide laboratories for 
the Psychiatric Department 



30,755 



Research laboratories for biolog- 41,054 
ical sciences, biophysics and 
psychology: provision. of built-in 
research equipment in new 
laboratory 



Basic Health research labora- 
tory: completion of new lab- 
oratories and installation of 
equipment 



649,312 



- 16 - 



INSTITUTION 

PENNSYLVANIA (continued) 

University of Penn- 
sylvania 
Philadelphia, Pa, 
Norman H. Topping, ¥uD, 

University of Penn- 
sylvania 
School of Dentistry 
Philadelphia, Pa. 



University. of Penn- 
sylvania 
Medical Division 
Philadelphia, Pa s 

Bryn Mawr College 
Bryn Mawr, Pa* 



The Woods School 
Langhorne, Pa. 

RHODE ISLAND 

Brown University 
Providence, Rhode 
Island 

TENNESSEE 

Vanderbilt University 
School of Medicine 
Nashville, Tenn, 



FACILITY MOUNT 



"The William H. Dormer Center ^YJ9,00k 
for Radiology" 



Research laboratories for School 150,000 
of Dentistry: (a) renovation of 
existing facilities and (b) new 
building consisting of a basement 
and two floors 

New research facilities for the 1+00,000 
School of Medicine: new 7-story 
research laboratory plus portions 
of two other new structures 

Biology research and teaching 300,000 
laboratory: new 3-story lab- 
oratory building 

Center for Child Study, Treat- 150,000 
ment and Research: new research 
laboratory building 



Psychology Laboratory: new ^11,002 
psychology laboratcrj' - for teach- 
ing and research 



Medical research facility: 173^5^8 
expansion, remodeling and 
equipping of health, research 
facilities 



UTAH 



University of Utah 
College of Medicine 
Salt Lake City, Utah 

Utah State Agricul- 
tural College 
Logan, Utah 



Basic medical research labora- 1,500,000 
tories : New medical science re- 
search building 

Research facilities for animal 26,157 
metabolism and nutrition studies : 
Expansion and remodeling of exist- 
ing animal research structure 



- 17 



INSTITUTION 



FACILITY 



AMOUNT 



VERMONT 



University of Vermont 
Burlington, Vermont 



WASHINGTON 

University of Washing- 
ton 
Seattle, Washington 

University of Washing- 
ton 
Seattle, Washington 

WISCONSIN 



Clinical and pathological re- 
search laboratories for the 
College of Medicine : new 2-story 
building 



Basic medical science research 
laboratories : remodeling and 
completion of existing structures 



$1*19,000 



155,000 



Research laboratory for psychol- 158,812 
ogy: remodeling of Denny Hall to 
provide research laboratories 



University of Wis- 
consin 
Medical School 
Madison, Wisconsin 



Clinical research facility: 975,000 
new 8-story research building 



2228<$3> 



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